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Entity

Name
AKT1
Namespace
HGNC
Namespace Version
20150611
Namespace URL
https://arty.scai.fraunhofer.de/artifactory/bel/namespace/hgnc-human-genes/hgnc-human-genes-20150601.belns

Appears in Networks 68

BEL Framework Large Corpus Document v20170611

Approximately 61,000 statements. This is a modified version of the original to use namespace files hosted on Artifactory

BEL Framework Small Corpus Document v20150611

Approximately 2000 hand curated statements drawn from 57 PubMeds.

Apoptosis-2.0-Hs v2.0

The Apoptosis network describes causal mechanisms in several different signaling pathways that are involved in the induction of apoptosis in response to environmental cues. The pathways include ER stress signaling, particularly the PERK-eIF2alpha-ATF4-CHOP pathway, MAPK components that regulate the pro-apoptotic proteins (Bad,Bax, Bim) via PI3K/AKT and JNK pathways, NFkB signaling which induces downstream expressions of anti-apoptotic proteins, PKC-mediated apoptosis, and activation of TNFR1 and Fas receptor leading to downstream signaling of caspase-8. The network also characterizes the transcriptional role of TP53 in apoptosis through the presence of its downstream anti-apoptotic and pro-apoptotic targets. \nReviewed during Jamboree2014

Autophagy-2.0-Hs v2.0

The Autophagy network depicts the causal mechanisms involved in the induction of autophagy following pulmonary tissue damage as a result of exposure to environmental insults. This includes the regulation of mTOR in the context of autophagy, ATG signaling that leads to autophagic vacuole formation, and regulation of protein translation via S6K and AMPK.

Endothelial Innate Immune Activation-2.0-Hs v2.0

The Endothelial Innate Immune Activation network depicts the causal mechanisms that describe acute response of healthy pulmonary endothelium to pro-inflammatory stimuli. These response mechanisms include production of the inflammatory chemokines, adhesion molecules and other mediators during endothelial cells activation leading to lung microvascular endothelial cells dysfunction. The network also includes causal mechanisms associated with angiogenic regulation by immune cells, including drivers of VEGF secretion and other related signaling pathways that crosstalk between the immune system and angiogenesis.

Fibrosis-2.0-Hs v2.0

The Fibrosis network depicts causal mechanisms that describe fibrosis and epithelial-to-mesenchymal cell transition (EMT) in lung tissue repair, including distinct characteristics of lung fibrosis such as TGFB1, collagen and MMPs. The network also contains signaling components of the Wnt, Hedgehog, and EGFR pathways that promote fibrosis and EMT.

Wound Healing-2.0-Hs v2.0

The Wound Healing network describes the causal mechanisms involved in the wound healing response in pulmonary tissue following exposure to cigarette smoke. This includes processes related to cell migration as a result of MMP degradation of matrix components and progenitor cell differentiation mediated by NOTCH1, SOX2, KRT14 and CTNNB1.

Apoptosis-2.0-Mm v2.0

The Apoptosis network describes causal mechanisms in several different signaling pathways that are involved in the induction of apoptosis in response to environmental cues. The pathways include ER stress signaling, particularly the PERK-eIF2alpha-ATF4-CHOP pathway, MAPK components that regulate the pro-apoptotic proteins (Bad,Bax, Bim) via PI3K/AKT and JNK pathways, NFkB signaling which induces downstream expressions of anti-apoptotic proteins, PKC-mediated apoptosis, and activation of TNFR1 and Fas receptor leading to downstream signaling of caspase-8. The network also characterizes the transcriptional role of TP53 in apoptosis through the presence of its downstream anti-apoptotic and pro-apoptotic targets. \nReviewed during Jamboree2014

Autophagy-2.0-Mm v2.0

The Autophagy network depicts the causal mechanisms involved in the induction of autophagy following pulmonary tissue damage as a result of exposure to environmental insults. This includes the regulation of mTOR in the context of autophagy, ATG signaling that leads to autophagic vacuole formation, and regulation of protein translation via S6K and AMPK.

Endothelial Innate Immune Activation-2.0-Mm v2.0

The Endothelial Innate Immune Activation network depicts the causal mechanisms that describe acute response of healthy pulmonary endothelium to pro-inflammatory stimuli. These response mechanisms include production of the inflammatory chemokines, adhesion molecules and other mediators during endothelial cells activation leading to lung microvascular endothelial cells dysfunction. The network also includes causal mechanisms associated with angiogenic regulation by immune cells, including drivers of VEGF secretion and other related signaling pathways that crosstalk between the immune system and angiogenesis.

Fibrosis-2.0-Mm v2.0

The Fibrosis network depicts causal mechanisms that describe fibrosis and epithelial-to-mesenchymal cell transition (EMT) in lung tissue repair, including distinct characteristics of lung fibrosis such as TGFB1, collagen and MMPs. The network also contains signaling components of the Wnt, Hedgehog, and EGFR pathways that promote fibrosis and EMT.

Wound Healing-2.0-Mm v2.0

The Wound Healing network describes the causal mechanisms involved in the wound healing response in pulmonary tissue following exposure to cigarette smoke. This includes processes related to cell migration as a result of MMP degradation of matrix components and progenitor cell differentiation mediated by NOTCH1, SOX2, KRT14 and CTNNB1.

Apoptosis-2.0-Rn v2.0

The Apoptosis network describes causal mechanisms in several different signaling pathways that are involved in the induction of apoptosis in response to environmental cues. The pathways include ER stress signaling, particularly the PERK-eIF2alpha-ATF4-CHOP pathway, MAPK components that regulate the pro-apoptotic proteins (Bad,Bax, Bim) via PI3K/AKT and JNK pathways, NFkB signaling which induces downstream expressions of anti-apoptotic proteins, PKC-mediated apoptosis, and activation of TNFR1 and Fas receptor leading to downstream signaling of caspase-8. The network also characterizes the transcriptional role of TP53 in apoptosis through the presence of its downstream anti-apoptotic and pro-apoptotic targets. \nReviewed during Jamboree2014

Autophagy-2.0-Rn v2.0

The Autophagy network depicts the causal mechanisms involved in the induction of autophagy following pulmonary tissue damage as a result of exposure to environmental insults. This includes the regulation of mTOR in the context of autophagy, ATG signaling that leads to autophagic vacuole formation, and regulation of protein translation via S6K and AMPK.

Endothelial Innate Immune Activation-2.0-Rn v2.0

The Endothelial Innate Immune Activation network depicts the causal mechanisms that describe acute response of healthy pulmonary endothelium to pro-inflammatory stimuli. These response mechanisms include production of the inflammatory chemokines, adhesion molecules and other mediators during endothelial cells activation leading to lung microvascular endothelial cells dysfunction. The network also includes causal mechanisms associated with angiogenic regulation by immune cells, including drivers of VEGF secretion and other related signaling pathways that crosstalk between the immune system and angiogenesis.

Fibrosis-2.0-Rn v2.0

The Fibrosis network depicts causal mechanisms that describe fibrosis and epithelial-to-mesenchymal cell transition (EMT) in lung tissue repair, including distinct characteristics of lung fibrosis such as TGFB1, collagen and MMPs. The network also contains signaling components of the Wnt, Hedgehog, and EGFR pathways that promote fibrosis and EMT.

Wound Healing-2.0-Rn v2.0

The Wound Healing network describes the causal mechanisms involved in the wound healing response in pulmonary tissue following exposure to cigarette smoke. This includes processes related to cell migration as a result of MMP degradation of matrix components and progenitor cell differentiation mediated by NOTCH1, SOX2, KRT14 and CTNNB1.

TBI_D1_CVBio_SCAI_8-3-2018 - QC v2.3.11

TBI BEL model is a disease model based on Biological Expression Language (BEL) containing the core mechanisms of Traumatic Brain Injury (TBI). This version contains knowledge extracted from 306 pubmed articles. This work is from the collaboration between CohenVeterans Bioscience and Fraunhofer SCAI.

TBI_D1_CVBio_SCAI_8-3-2018 - QC v2.3.14

TBI BEL model is a disease model based on Biological Expression Language (BEL) containing the core mechanisms of Traumatic Brain Injury (TBI). This version contains knowledge extracted from 306 pubmed articles. This work is from the collaboration between CohenVeterans Bioscience and Fraunhofer SCAI.

TBI_D1_CVBio_SCAI_8-3-2018 - QC v2.3.15

TBI BEL model is a disease model based on Biological Expression Language (BEL) containing the core mechanisms of Traumatic Brain Injury (TBI). This version contains knowledge extracted from 306 pubmed articles. This work is from the collaboration between CohenVeterans Bioscience and Fraunhofer SCAI.

TBI_D1_CVBio_SCAI_8-3-2018 - QC v2.3.16

TBI BEL model is a disease model based on Biological Expression Language (BEL) containing the core mechanisms of Traumatic Brain Injury (TBI). This version contains knowledge extracted from 306 pubmed articles. This work is from the collaboration between CohenVeterans Bioscience and Fraunhofer SCAI.

Alzheimer's Disease Knowledge Assembly v5.0.4

This knowledge assembly is specific to Alzheimer's Disease for the AETIONOMY project. It encodes the pathological mechanisms in neurons in the human brain as well as additional evidence from mice and rats. This model includes different pathways such as apoptosis signaling, calcium signaling, cholesterol homeostasis, endocytosis, GSK activation, inflammatory responses, oxidative stress of mitochondria and endoplasmic reticulum, etc. In this version, we have added additional mechanisms/pathways to describe the functional consequences of SNPs linked with genes implicated in Alzheimer's Disease through GWAS.

TBI_D1_CVBio_SCAI_8-3-2018 - QC v2.3.18

TBI BEL model is a disease model based on Biological Expression Language (BEL) containing the core mechanisms of Traumatic Brain Injury (TBI). This version contains knowledge extracted from 306 pubmed articles. This work is from the collaboration between CohenVeterans Bioscience and Fraunhofer SCAI.

TBI_D1_CVBio_SCAI_8-3-2018 - QC v2.3.19

TBI BEL model is a disease model based on Biological Expression Language (BEL) containing the core mechanisms of Traumatic Brain Injury (TBI). This version contains knowledge extracted from 306 pubmed articles. This work is from the collaboration between CohenVeterans Bioscience and Fraunhofer SCAI.

TBI_D1_CVBio_SCAI_8-3-2018 - QC v2.3.20

TBI BEL model is a disease model based on Biological Expression Language (BEL) containing the core mechanisms of Traumatic Brain Injury (TBI). This version contains knowledge extracted from 306 pubmed articles. This work is from the collaboration between CohenVeterans Bioscience and Fraunhofer SCAI.

TBI_D1_CVBio_SCAI_8-3-2018 - QC v2.3.21

TBI BEL model is a disease model based on Biological Expression Language (BEL) containing the core mechanisms of Traumatic Brain Injury (TBI). This version contains knowledge extracted from 306 pubmed articles. This work is from the collaboration between CohenVeterans Bioscience and Fraunhofer SCAI.

TBI_D1_CVBio_SCAI_8-3-2018 - QC v2.3.22

TBI BEL model is a disease model based on Biological Expression Language (BEL) containing the core mechanisms of Traumatic Brain Injury (TBI). This version contains knowledge extracted from 306 pubmed articles. This work is from the collaboration between CohenVeterans Bioscience and Fraunhofer SCAI.

TBI_D1_CVBio_SCAI_8-3-2018 - QC v2.3.23

TBI BEL model is a disease model based on Biological Expression Language (BEL) containing the core mechanisms of Traumatic Brain Injury (TBI). This version contains knowledge extracted from 306 pubmed articles. This work is from the collaboration between CohenVeterans Bioscience and Fraunhofer SCAI.

TBI_D1_CVBio_SCAI_8-3-2018 - QC v2.3.26

TBI BEL model is a disease model based on Biological Expression Language (BEL) containing the core mechanisms of Traumatic Brain Injury (TBI). This version contains knowledge extracted from 306 pubmed articles. This work is from the collaboration between CohenVeterans Bioscience and Fraunhofer SCAI.

TBI_D1_CVBio_SCAI_8-3-2018 - QC v2.3.27

TBI BEL model is a disease model based on Biological Expression Language (BEL) containing the core mechanisms of Traumatic Brain Injury (TBI). This version contains knowledge extracted from 306 pubmed articles. This work is from the collaboration between CohenVeterans Bioscience and Fraunhofer SCAI.

TBI_D1_CVBio_SCAI_8-3-2018 - QC v2.3.28

TBI BEL model is a disease model based on Biological Expression Language (BEL) containing the core mechanisms of Traumatic Brain Injury (TBI). This version contains knowledge extracted from 306 pubmed articles. This work is from the collaboration between CohenVeterans Bioscience and Fraunhofer SCAI.

TBI_D1_CVBio_SCAI_13-04-2018 v2.3.28

TBI BEL model is a disease model based on Biological Expression Language (BEL) containing the core mechanisms of Traumatic Brain Injury (TBI). This version contains knowledge extracted from 306 pubmed articles. This work is from the collaboration between CohenVeterans Bioscience and Fraunhofer SCAI.

TBI_D1_CVBio_SCAI_19-04-2018 v2.3.30

TBI BEL model is a disease model based on Biological Expression Language (BEL) containing the core mechanisms of Traumatic Brain Injury (TBI). This version contains knowledge extracted from 306 pubmed articles. This work is from the collaboration between CohenVeterans Bioscience and Fraunhofer SCAI.

TBI_D1_CVBio_SCAI_22-04-2018 v2.3.31

TBI BEL model is a disease model based on Biological Expression Language (BEL) containing the core mechanisms of Traumatic Brain Injury (TBI). This version contains knowledge extracted from 306 pubmed articles. This work is from the collaboration between CohenVeterans Bioscience and Fraunhofer SCAI.

TBI_D1_CVBio_SCAI_22-04-2018 v2.3.32

TBI BEL model is a disease model based on Biological Expression Language (BEL) containing the core mechanisms of Traumatic Brain Injury (TBI). This version contains knowledge extracted from 306 pubmed articles. This work is from the collaboration between CohenVeterans Bioscience and Fraunhofer SCAI.

TBI_D1_CVBio_SCAI_25-04-2018 v2.3.33

TBI BEL model is a disease model based on Biological Expression Language (BEL) containing the core mechanisms of Traumatic Brain Injury (TBI). This version contains knowledge extracted from 306 pubmed articles. This work is from the collaboration between CohenVeterans Bioscience and Fraunhofer SCAI.

PTSD BEL Model Versions 1 and 2 - Re-Reviewed v1.0.0

PTSD BEL model is a disease model based on Biological Expression Language (BEL) containing the core mechanisms of Post Traumatic Stress Disorder (PTSD). This version contains knowledge extracted from 348 pubmed articles and 2 articles from other sources like Book. This work is from the collaboration between CohenVeterans Bioscience and Fraunhofer SCAI

PTSD and TBI BEL Model v1.0.1

PTSD BEL model is a disease model based on Biological Expression Language (BEL) containing the core mechanisms of Post Traumatic Stress Disorder (PTSD). This version contains knowledge extracted from 348 pubmed articles and 2 articles from other sources like Book. This work is from the collaboration between CohenVeterans Bioscience and Fraunhofer SCAI

PTSD and TBI BEL Model v1.0.8

PTSD BEL model is a disease model based on Biological Expression Language (BEL) containing the core mechanisms of Post Traumatic Stress Disorder (PTSD). This version contains knowledge extracted from 348 pubmed articles and 2 articles from other sources like Book. This work is from the collaboration between CohenVeterans Bioscience and Fraunhofer SCAI

PTSD and TBI BEL Model v1.0.9

PTSD BEL model is a disease model based on Biological Expression Language (BEL) containing the core mechanisms of Post Traumatic Stress Disorder (PTSD). This version contains knowledge extracted from 348 pubmed articles and 2 articles from other sources like Book. This work is from the collaboration between CohenVeterans Bioscience and Fraunhofer SCAI

PTSD and TBI BEL Model v1.0.10

PTSD BEL model is a disease model based on Biological Expression Language (BEL) containing the core mechanisms of Post Traumatic Stress Disorder (PTSD). This version contains knowledge extracted from 348 pubmed articles and 2 articles from other sources like Book. This work is from the collaboration between CohenVeterans Bioscience and Fraunhofer SCAI

PTSD and TBI BEL Model v1.0.11

PTSD BEL model is a disease model based on Biological Expression Language (BEL) containing the core mechanisms of Post Traumatic Stress Disorder (PTSD). This version contains knowledge extracted from 348 pubmed articles and 2 articles from other sources like Book. This work is from the collaboration between CohenVeterans Bioscience and Fraunhofer SCAI

PTSD and TBI BEL Model v1.0.12

PTSD BEL model is a disease model based on Biological Expression Language (BEL) containing the core mechanisms of Post Traumatic Stress Disorder (PTSD). This version contains knowledge extracted from 348 pubmed articles and 2 articles from other sources like Book. This work is from the collaboration between CohenVeterans Bioscience and Fraunhofer SCAI

PTSD and TBI BEL Model v1.0.15

PTSD BEL model is a disease model based on Biological Expression Language (BEL) containing the core mechanisms of Post Traumatic Stress Disorder (PTSD). This version contains knowledge extracted from 348 pubmed articles and 2 articles from other sources like Book. This work is from the collaboration between CohenVeterans Bioscience and Fraunhofer SCAI

PTSD and TBI BEL Model v1.0.16

PTSD BEL model is a disease model based on Biological Expression Language (BEL) containing the core mechanisms of Post Traumatic Stress Disorder (PTSD). This version contains knowledge extracted from 348 pubmed articles and 2 articles from other sources like Book. This work is from the collaboration between CohenVeterans Bioscience and Fraunhofer SCAI

PTSD and TBI BEL Model v1.0.17

PTSD BEL model is a disease model based on Biological Expression Language (BEL) containing the core mechanisms of Post Traumatic Stress Disorder (PTSD). This version contains knowledge extracted from 348 pubmed articles and 2 articles from other sources like Book. This work is from the collaboration between CohenVeterans Bioscience and Fraunhofer SCAI

PTSD and TBI BEL Model v1.0.20

PTSD BEL model is a disease model based on Biological Expression Language (BEL) containing the core mechanisms of Post Traumatic Stress Disorder (PTSD). This version contains knowledge extracted from 348 pubmed articles and 2 articles from other sources like Book. This work is from the collaboration between CohenVeterans Bioscience and Fraunhofer SCAI

Colorectal Cancer Knowledge Assembly - Drugs Pathways and General Biology v1.1.0

Colorectal Cancer Knowledge Assembly with drug associations and Pathways + general CRC biology

PTSD and TBI BEL Model v1.0.22

PTSD BEL model is a disease model based on Biological Expression Language (BEL) containing the core mechanisms of Post Traumatic Stress Disorder (PTSD). This version contains knowledge extracted from 348 pubmed articles and 2 articles from other sources like Book. This work is from the collaboration between CohenVeterans Bioscience and Fraunhofer SCAI

PTSD and TBI BEL Model v1.0.23

PTSD BEL model is a disease model based on Biological Expression Language (BEL) containing the core mechanisms of Post Traumatic Stress Disorder (PTSD). This version contains knowledge extracted from 348 pubmed articles and 2 articles from other sources like Book. This work is from the collaboration between CohenVeterans Bioscience and Fraunhofer SCAI

PTSD and TBI BEL Model v1.0.24

PTSD BEL model is a disease model based on Biological Expression Language (BEL) containing the core mechanisms of Post Traumatic Stress Disorder (PTSD). This version contains knowledge extracted from 348 pubmed articles and 2 articles from other sources like Book. This work is from the collaboration between CohenVeterans Bioscience and Fraunhofer SCAI

PTSD and TBI BEL Model v1.0.25

PTSD BEL model is a disease model based on Biological Expression Language (BEL) containing the core mechanisms of Post Traumatic Stress Disorder (PTSD). This version contains knowledge extracted from 348 pubmed articles and 2 articles from other sources like Book. This work is from the collaboration between CohenVeterans Bioscience and Fraunhofer SCAI

TBI BEL Model v1.0.27

TBI BEL model is a disease model based on Biological Expression Language (BEL) containing the core mechanisms of Traumatic Brain Injury. This version contains knowledge extracted from 523 pubmed articles. This work is from the collaboration between CohenVeterans Bioscience and Fraunhofer SCAI

TBRD - PTSD and TBI BEL Model v1.0.30

TBRD BEL model is a disease model based on Biological Expression Language (BEL) containing the core mechanisms of Post Traumatic Stress Disorder (PTSD) and Traumatic Brain Injury (TBI). This version contains knowledge extracted from 847 pubmed articles and 2 articles from other sources like Book. Out of these,523 articles belongs 323 PTSD articles. This work is from the collaboration between CohenVeterans Bioscience and Fraunhofer SCAI

Alzheimer's Disease Knowledge Assembly v5.0.6

This knowledge assembly is specific to Alzheimer's Disease for the AETIONOMY project. It encodes the pathological mechanisms in neurons in the human brain as well as additional evidence from mice and rats. This model includes different pathways such as apoptosis signaling, calcium signaling, cholesterol homeostasis, endocytosis, GSK activation, inflammatory responses, oxidative stress of mitochondria and endoplasmic reticulum, etc. In this version, we have added additional mechanisms/pathways to describe the functional consequences of SNPs linked with genes implicated in Alzheimer's Disease through GWAS.

Alzheimer's Disease Knowledge Assembly v5.0.9

This knowledge assembly is specific to Alzheimer's Disease for the AETIONOMY project. It encodes the pathological mechanisms in neurons in the human brain as well as additional evidence from mice and rats. This model includes different pathways such as apoptosis signaling, calcium signaling, cholesterol homeostasis, endocytosis, GSK activation, inflammatory responses, oxidative stress of mitochondria and endoplasmic reticulum, etc. In this version, we have added additional mechanisms/pathways to describe the functional consequences of SNPs linked with genes implicated in Alzheimer's Disease through GWAS.

colorectal cancer Knowledge Assembly - Drugs v1.0.1

colorectal cancer Knowledge Assembly with drug associations.

Colorectal Cancer Model v1.0.0

Colorectal Cancer Model built for i:DSem-BMBF project.

colorectal cancer Drugs resistance v1.0.1.0

colorectal cancer Knowledge Assembly with drug associations.

CRC_combined v1.1

BEL Document

Colorectal Cancer Model v2.0.0

Colorectal Cancer Model

Colorectal Cancer Model v0.0.0

Colorectal Cancer Model

Colorectal Cancer Model v2.0.3

Colorectal Cancer Model

Colorectal Cancer Model v2.0.4

Colorectal Cancer Model, uploaded by reagon

Colorectal Cancer Model v2.0.5

Colorectal Cancer Model, uploaded by reagon

Colorectal Cancer Model v2.0.6

Colorectal Cancer Model, uploaded by reagon

Anatabine v1.0

BEL Document

In-Edges 73

p(HGNC:IRS1) increases p(HGNC:AKT1, pmod(Ph, Ser, 473))

IRS-1 knockdown in both cell lines resulted in reduction of insulin stimulated Akt1 phosphorylation at Ser 473. In parental HepG2 cells, IRS-1 knockdown resulted in reduction (ca. 50%) in the basal level of phosphorylated mTOR (Ser 2448) irrespective of insulin treatment. PubMed:17721885

Annotations
Experimental Factor Ontology (EFO)
Hep G2 cell
NCBI Taxonomy Ids
9606
Uberon
bone marrow
Cell Ontology (CL)
fat cell
MeSH
Cell Nucleus
Disease Ontology (DO)
breast cancer
MeSH
Sputum
MeSH
Head and Neck Neoplasms

act(complex(SCOMP:"p85/p110 PI3Kinase Complex"), ma(kin)) increases p(HGNC:AKT1, pmod(Ph, Ser, 473))

Overexpressed IRS-3 as well as IRS-1 enhanced phosphoinositide (PI) 3-kinase activity in response to insulin and increased phosphorylation of protein kinase B (PKB) at S473 and phosphorylation of one of the members of the forkhead transcription factor FKHRL1 on T32 in both insulin-untreated and -treated states. PubMed:12504093

Annotations
Experimental Factor Ontology (EFO)
NIH-3T3 cell
NCBI Taxonomy Ids
9606
Uberon
heart
Cell Ontology (CL)
hepatocyte
MeSH
Cell Membrane
Disease Ontology (DO)
atherosclerosis

act(complex(SCOMP:"p85/p110 PI3Kinase Complex"), ma(kin)) increases p(HGNC:AKT1, pmod(Ph, Ser, 473))

These results suggest that PI3K mediates T3-dependent activation of Akt/PKB, mTOR, and p70S6K. More importantly it indicates that T3-dependent PI3K activation is an initial event leading to the activation of Akt/PKB, mTOR, and p70S6K. PubMed:15388791

Annotations
Experimental Factor Ontology (EFO)
A549 cell
NCBI Taxonomy Ids
9606
Uberon
zone of skin
Cell Ontology (CL)
fibroblast
MeSH
Extracellular Space
Disease Ontology (DO)
lung cancer
MeSH
Hypercholesterolemia

act(complex(SCOMP:"p85/p110 PI3Kinase Complex"), ma(kin)) increases p(HGNC:AKT1, pmod(Ph, Ser, 473))

Exposure of cells to alpha2M* (50 pM) induced phosphatidylinositol 3-kinase-dependent activation of Akt by phosphorylation at Thr-308 and Ser-473 with a concomitant 60-80% increase in Akt-associated kinase activity. ERK1/2 and p38 MAPK were also activated PubMed:16543232

Annotations
Experimental Factor Ontology (EFO)
293 cell
NCBI Taxonomy Ids
9606
Uberon
smooth muscle tissue
Cell Ontology (CL)
endothelial cell
MeSH
Golgi Apparatus
Disease Ontology (DO)
prostate cancer
MeSH
Sputum
MeSH
Head and Neck Neoplasms

act(complex(SCOMP:"p85/p110 PI3Kinase Complex"), ma(kin)) increases p(HGNC:AKT1, pmod(Ph, Ser, 473))

Akt activation is dependent on its phosphorylation at Thr308 and Ser473. The mechanism by which thrombin induces Akt phosphorylation is controversial, as is the role of Akt in platelet function.Platelet PAR stimulation causes rapid Akt phosphorylation downstream of PLC; while in the continuous stimulation, ADP and PI3K are required for maintaining Akt phosphorylation. PubMed:17883592

Annotations
Experimental Factor Ontology (EFO)
MDA-MB-231 cell
NCBI Taxonomy Ids
9606
Uberon
adipose tissue
Cell Ontology (CL)
platelet
MeSH
Cell Nucleus
Disease Ontology (DO)
non-small cell lung carcinoma
MeSH
Sputum
MeSH
Head and Neck Neoplasms

act(complex(SCOMP:"p85/p110 PI3Kinase Complex"), ma(kin)) increases p(HGNC:AKT1, pmod(Ph, Ser, 473))

Pam3CSK4 dose-dependently increased Akt phosphorylation at serine 473 (Figure 3A), and preincubation with TLR2-blocking antibody reduced Pam3CSK4-induced Akt phosphorylation (Figure 3B). Preincubation with LY294002, a specific inhibitor of PI3-K, also dose-dependently inhibited Akt phosphorylation (Figure 3C). PubMed:19106411

Annotations
Experimental Factor Ontology (EFO)
WI-38 cell
NCBI Taxonomy Ids
9606
Uberon
prostate gland
Cell Ontology (CL)
platelet
MeSH
Extracellular Matrix
Disease Ontology (DO)
lung cancer
MeSH
Sputum
MeSH
Head and Neck Neoplasms

act(complex(SCOMP:"p85/p110 PI3Kinase Complex"), ma(kin)) increases p(HGNC:AKT1, pmod(Ph, Ser, 473))

FIGURE 3. Amino acids induce Akt phosphorylations (Thr-308,Ser-473) via class I PI3K PubMed:21131356

Annotations
Experimental Factor Ontology (EFO)
HeLa cell
NCBI Taxonomy Ids
9606
Uberon
respiratory airway
Cell Ontology (CL)
epithelial cell
MeSH
Cell Membrane
Disease Ontology (DO)
glioblastoma multiforme
MeSH
Sputum
MeSH
Head and Neck Neoplasms

p(HGNC:BTC) increases p(HGNC:AKT1, pmod(Ph, Ser, 473))

BTC induced ERK1/2 and Akt phosphorylation in a dose- and time-dependent manner. BTC induced phosphorylation of all three EGF receptors present on HUVECs: ErbB2, ErbB3, and ErbB4. Antibodies for phospho-specific ERK1/2 (Thr202/Tyr204) and phospho-specific Akt (Ser473) were purchased form New England Biolabs (Beverly, MA). PubMed:12475887

Annotations
Experimental Factor Ontology (EFO)
HUVEC cell line
NCBI Taxonomy Ids
9606
Uberon
breast
Cell Ontology (CL)
epithelial cell
MeSH
Cell Membrane
Disease Ontology (DO)
neuroblastoma

p(HGNC:EGF) increases p(HGNC:AKT1, pmod(Ph, Ser, 473))

We employed well established PI3K inhibitors, wortmannin and LY294002, to blunt the PI3K signaling pathway. The phosphorylation of Akt induced by EGF was totally abolished by preincubation with the PI3K inhibitors in TE-2, TE-8, and TE-10 cells (Fig. 6). PubMed:10908564

Annotations
Experimental Factor Ontology (EFO)
MEF cell line
NCBI Taxonomy Ids
9606
Uberon
esophagus
Cell Ontology (CL)
bronchial epithelial cell
MeSH
Cell Nucleus
Disease Ontology (DO)
esophageal carcinoma

p(HGNC:EGF) increases p(HGNC:AKT1, pmod(Ph, Ser, 473))

Western blotting with the anti-phospho-Akt1 antibody, which recognizes only phosphorylated Ser-473 residue, was performed in human esophageal cancer cell lines (TE-2, TE-5, TE-8, TE-9, TE-10, and TE-12 cells) (top panel). PDGF-treated NIH3T3 cells served as a positive control. The phospho-Akt antibody demonstrated two bands at 60 kDa. The phosphorylation of Akt was enhanced by EGF stimulation in all the esophageal cancer cell lines examined, although TE-5 cells showed high basal phosphorylation of Akt. PubMed:10908564

Annotations
Experimental Factor Ontology (EFO)
MEF cell line
NCBI Taxonomy Ids
9606
Uberon
esophagus
Cell Ontology (CL)
bronchial epithelial cell
MeSH
Cell Nucleus
Disease Ontology (DO)
esophageal carcinoma

act(p(HGNC:OLR1), ma(cat)) decreases p(HGNC:AKT1, pmod(Ph, Ser, 473))

Pretreatment of EPCs at day 3 with 10 mg/ ml TS20, however, protected against L5-induced reductions of phosphorylated Akt (Fig. 9). PubMed:17909223

Annotations
Experimental Factor Ontology (EFO)
MCF 10A cell
NCBI Taxonomy Ids
9606
Uberon
lung
Cell Ontology (CL)
adult endothelial progenitor cell
MeSH
Cell Nucleus
Disease Ontology (DO)
colon cancer
MeSH
Sputum
MeSH
Head and Neck Neoplasms

act(p(HGNC:MET), ma(kin)) increases p(HGNC:AKT1, pmod(Ph, Ser, 473))

Figure 6A PubMed:17667909

Annotations
Experimental Factor Ontology (EFO)
NCI-H69 cell
NCBI Taxonomy Ids
9606
Uberon
lung
Cell Ontology (CL)
keratinocyte
MeSH
Cytoplasm
Disease Ontology (DO)
lung cancer
MeSH
Sputum
MeSH
Head and Neck Neoplasms

p(HGNC:HGF) increases p(HGNC:AKT1, pmod(Ph, Ser, 473))

As shown in Fig. 4C, SU11274 also inhibited HGF-induced phosphorylation of AKT and ERK1/2 in a dose-dependent manner. PubMed:16397249

Annotations
Experimental Factor Ontology (EFO)
HUVEC cell line
NCBI Taxonomy Ids
9606
Uberon
smooth muscle tissue
Cell Ontology (CL)
neuron
MeSH
Cytoplasm
Disease Ontology (DO)
non-small cell lung carcinoma
MeSH
Sputum
MeSH
Head and Neck Neoplasms

p(HGNC:HGF) increases p(HGNC:AKT1, pmod(Ph, Ser, 473))

As shown in Fig. 4C, SU11274 also inhibited HGF-induced phosphorylation of AKT and ERK1/2 in a dose-dependent manner. PubMed:16397249

Annotations
Experimental Factor Ontology (EFO)
HUVEC cell line
NCBI Taxonomy Ids
9606
Uberon
epithelium
Cell Ontology (CL)
neuron
MeSH
Cytoplasm
Disease Ontology (DO)
lung cancer
MeSH
Sputum
MeSH
Head and Neck Neoplasms

p(HGNC:HGF) increases p(HGNC:AKT1, pmod(Ph, Ser, 473))

MPM cells were responsive to HGF (40 ng/mL) stimulation of c-Met signaling up to 5 hours in a time-dependent fashion (Fig. 2B). Significant induction of tyrosine phosphorylation in c-Met of the autophosphorylation site (pY1230/1234/1235) as well as the regulatory juxtamembrane c-Cbl binding site (pY1003) was evident starting at 15 minutes of HGF stimulation and the phospho-signal declined between 2 and 5 hours. Moreover, phosphorylation of ERK1/2 (pT185/pY187) and AKT (S473) was significantly induced in a differential manner with different cell lines after HGF stimulation (Fig. 2B). PubMed:16397249

Annotations
Experimental Factor Ontology (EFO)
HUVEC cell line
NCBI Taxonomy Ids
9606
Uberon
epithelium
Cell Ontology (CL)
neuron
MeSH
Cytoplasm
Disease Ontology (DO)
lung cancer
MeSH
Sputum
MeSH
Head and Neck Neoplasms

p(HGNC:HGF) increases p(HGNC:AKT1, pmod(Ph, Ser, 473))

In c-MET-overexpressing SCLC cell line NCI-H69, hepatocyte growth factor (HGF) dramatically induced c-MET phosphorylation at phosphoepitopes pY1230/1234/1235 (catalytic tyrosine kinase), pY1003 (juxtamembrane), and also of paxillin at pY31 (CRKL-binding site). We utilised a global proteomics phosphoantibody array approach to identify further c-MET/HGF signal transduction intermediates in SCLC. Strong HGF induction of specific phosphorylation sites in phosphoproteins involved in c-MET/HGF signal transduction was detected, namely adducin-alpha [S724], adducin-gamma [S662], CREB [S133], ERK1 [T185/Y187], ERK1/2 [T202/Y204], ERK2 [T185/Y187], MAPKK (MEK) 1/2 [S221/S225], MAPKK (MEK) 3/6 [S189/S207], RB [S612], RB1 [S780], JNK [T183/Y185], STAT3 [S727], focal adhesion kinase (FAK) [Y576/S722/S910], p38alpha-MAPK [T180/Y182], and AKT1[S473] and [T308]. Conversely, we also identified modest inhibition of phosphorylation by HGF in the following phosphoproteins (Figures 2A and B): PKCa [S657], PKCa/b [T368/641], and PKCd [T505]. Moreover, HGF also inhibited phosphorylation of PKR [T451], which is known to have antiproliferative and pro-apoptotic functions. Lastly, HGF also reduced the threonine and tyrosine phosphorylation of the cell cycle checkpoint regulator CDK1 [T14/Y15]. PubMed:17667909

Annotations
Experimental Factor Ontology (EFO)
NCI-H69 cell
NCBI Taxonomy Ids
9606
Uberon
lung
Cell Ontology (CL)
keratinocyte
MeSH
Cytoplasm
Disease Ontology (DO)
lung cancer
MeSH
Sputum
MeSH
Head and Neck Neoplasms

p(HGNC:HGF) increases p(HGNC:AKT1, pmod(Ph, Ser, 473))

Cigarette smoke inhibits phosphorylation of AKT Ser 473 in a time-dependent manner although it was not statistically significant (Figs. 4A and C). In contrast, HGF-induced phosphorylation of AKT Ser 473 PubMed:20850432

Annotations
Experimental Factor Ontology (EFO)
immortal cell line cell
NCBI Taxonomy Ids
9606
Uberon
coronary artery
Cell Ontology (CL)
bronchial epithelial cell
MeSH
Cell Membrane
Disease Ontology (DO)
glioblastoma multiforme
MeSH
Sputum
MeSH
Head and Neck Neoplasms

act(p(HGNC:ILK), ma(kin)) directlyIncreases p(HGNC:AKT1, pmod(Ph, Ser, 473))

Activation of PKB alpha and beta is then achieved at the plasma membrane by phosphorylation of Thr308/309 in the A-loop of the kinase domain and Ser473/474 in the carboxy-terminal regulatory region, respectively. The upstream kinase that phosphorylates PKB on Thr308, termed PI-dependent protein kinase-1, has been identified and extensively characterised. A candidate for the Ser473/474 kinase, termed the integrin-linked kinase, has been identified recently. PubMed:10454216

Annotations
Experimental Factor Ontology (EFO)
U-937 cell
NCBI Taxonomy Ids
9606
Uberon
skeletal muscle tissue
Cell Ontology (CL)
macrophage
MeSH
Cell Membrane
Disease Ontology (DO)
leukemia

act(p(HGNC:ILK), ma(kin)) directlyIncreases p(HGNC:AKT1, pmod(Ph, Ser, 473))

11313365;10226025 PubMed:15212693

Annotations
Experimental Factor Ontology (EFO)
COS-1 cell
NCBI Taxonomy Ids
9606
Uberon
epithelium
Cell Ontology (CL)
fibroblast
MeSH
Cell Nucleus
Disease Ontology (DO)
non-small cell lung carcinoma

p(HGNC:KITLG) increases p(HGNC:AKT1, pmod(Ph, Ser, 473))

Stem cell factor (SCF) induced phosphorylation of PKB at Thr308 and Ser473 in H-69, H-209 and H-510 cells. Dominant negative form of PI3KC2B impaired SCF induced PKB activation. PubMed:12356726

Annotations
Experimental Factor Ontology (EFO)
MCF7 cell
NCBI Taxonomy Ids
9606
Uberon
blood plasma
Cell Ontology (CL)
macrophage
MeSH
Cell Nucleus
Disease Ontology (DO)
lung cancer

p(HGNC:F2) increases p(HGNC:AKT1, pmod(Ph, Ser, 473))

Thrombin induces the activation of platelet serine/threonine kinase Akt. Akt activation is dependent on its phosphorylation at threonine 308 and serine 473. PubMed:17883592

Annotations
Experimental Factor Ontology (EFO)
MDA-MB-231 cell
NCBI Taxonomy Ids
9606
Uberon
adipose tissue
Cell Ontology (CL)
platelet
MeSH
Cell Nucleus
Disease Ontology (DO)
non-small cell lung carcinoma
MeSH
Sputum
MeSH
Head and Neck Neoplasms

p(HGNC:AKT1) hasVariant p(HGNC:AKT1, pmod(Ph, Ser, 473))

Appears in Networks:

m(HGNC:MIR155) increases p(HGNC:AKT1, pmod(Ph, Ser, 473))

Reducing expression of miR-21 or miR-155 led to upregulation of phosphatase and tensin homologue (PTEN), programmed cell death 4 (PDCD4), or Src homology-2 domain-containing inositol 5-phosphatase 1 (SHIP1). ASO-21- and ASO-155-treated cell lines all showed downregulation of phosphorylated AKT(ser473) (pAKT). Moreover, transduction with either miR-21 or miR-155 led to downregulation of PTEN and PDCD4, or SHIP1 with upregulation of pAKT. PubMed:19641183

Annotations
Experimental Factor Ontology (EFO)
HaCaT
NCBI Taxonomy Ids
9606
Uberon
liver
Cell Ontology (CL)
fibroblast
MeSH
Extracellular Matrix
Disease Ontology (DO)
hematologic cancer
MeSH
Sputum
MeSH
Head and Neck Neoplasms

act(p(EGID:2475), ma(kin)) decreases p(HGNC:AKT1, pmod(Ph, Ser, 473))

Furthermore, we show that inhibition of mTOR by rapamycin induces the activation of Akt as shown by increased Akt phosphorylation at Ser(473) and the inhibition of 6-TG-induced apoptosis and cell death. Activated Akt is a well-known inhibitor of autophagy. PubMed:18381446

Annotations
Experimental Factor Ontology (EFO)
NCI-H292 cell
NCBI Taxonomy Ids
9606
Uberon
cardiac ventricle
Cell Ontology (CL)
bronchial epithelial cell
MeSH
Cell Nucleus
Disease Ontology (DO)
leukemia
MeSH
Sputum
MeSH
Head and Neck Neoplasms

m(HGNC:MIR21) increases p(HGNC:AKT1, pmod(Ph, Ser, 473))

Reducing expression of miR-21 or miR-155 led to upregulation of phosphatase and tensin homologue (PTEN), programmed cell death 4 (PDCD4), or Src homology-2 domain-containing inositol 5-phosphatase 1 (SHIP1). ASO-21- and ASO-155-treated cell lines all showed downregulation of phosphorylated AKT(ser473) (pAKT). Moreover, transduction with either miR-21 or miR-155 led to downregulation of PTEN and PDCD4, or SHIP1 with upregulation of pAKT. PubMed:19641183

Annotations
Experimental Factor Ontology (EFO)
HaCaT
NCBI Taxonomy Ids
9606
Uberon
liver
Cell Ontology (CL)
fibroblast
MeSH
Extracellular Matrix
Disease Ontology (DO)
hematologic cancer
MeSH
Sputum
MeSH
Head and Neck Neoplasms

p(HGNC:IGF1) increases p(HGNC:AKT1, pmod(Ph, Ser, 473))

To determine whether PKA-induced PKB activation accounts for GSK-3 phosphorylation after treatment with 8-Br-cAMP, forskolin, or isoproterenol, PKB phosphorylation at serine 473 and threonine 308, which is crucial for activation of PKB (20), was assessed. As expected, insulin and IGF-1 strongly stimulated phosphorylation of PKB at serine 473 in NIH 3T3 or Rat1 cells (Fig. 2B). In contrast, 8-Br-cAMP, forskolin, and isoproterenol did not significantly alter PKB phosphorylation at serine 473 (Fig. 2B). Similar results were obtained with a threonine 308 phosphorylation-specific antibody (data not shown). PubMed:11035810

Annotations
Experimental Factor Ontology (EFO)
MCF7 cell
NCBI Taxonomy Ids
10090
Uberon
kidney
Cell Ontology (CL)
neutrophil
MeSH
Cytoplasm
Disease Ontology (DO)
cancer
MeSH
Macrophages

p(HGNC:IGF1) increases p(HGNC:AKT1, pmod(Ph, Ser, 473))

To determine whether PKA-induced PKB activation accounts for GSK-3 phosphorylation after treatment with 8-Br-cAMP, forskolin, or isoproterenol, PKB phosphorylation at serine 473 and threonine 308, which is crucial for activation of PKB (20), was assessed. As expected, insulin and IGF-1 strongly stimulated phosphorylation of PKB at serine 473 in NIH 3T3 or Rat1 cells (Fig. 2B). In contrast, 8-Br-cAMP, forskolin, and isoproterenol did not significantly alter PKB phosphorylation at serine 473 (Fig. 2B). Similar results were obtained with a threonine 308 phosphorylation-specific antibody (data not shown). PubMed:11035810

Annotations
Experimental Factor Ontology (EFO)
MCF7 cell
NCBI Taxonomy Ids
10116
Uberon
kidney
Cell Ontology (CL)
neutrophil
MeSH
Cytoplasm
Disease Ontology (DO)
cancer
MeSH
Macrophages

a(CHEBIID:50864) increases p(HGNC:AKT1, pmod(Ph, Ser, 473))

To determine whether PKA-induced PKB activation accounts for GSK-3 phosphorylation after treatment with 8-Br-cAMP, forskolin, or isoproterenol, PKB phosphorylation at serine 473 and threonine 308, which is crucial for activation of PKB (20), was assessed. As expected, insulin and IGF-1 strongly stimulated phosphorylation of PKB at serine 473 in NIH 3T3 or Rat1 cells (Fig. 2B). In contrast, 8-Br-cAMP, forskolin, and isoproterenol did not significantly alter PKB phosphorylation at serine 473 (Fig. 2B). Similar results were obtained with a threonine 308 phosphorylation-specific antibody (data not shown). PubMed:11035810

Annotations
Experimental Factor Ontology (EFO)
MCF7 cell
NCBI Taxonomy Ids
10090
Uberon
kidney
Cell Ontology (CL)
neutrophil
MeSH
Cytoplasm
Disease Ontology (DO)
cancer
MeSH
Macrophages

a(CHEBIID:50864) increases p(HGNC:AKT1, pmod(Ph, Ser, 473))

To determine whether PKA-induced PKB activation accounts for GSK-3 phosphorylation after treatment with 8-Br-cAMP, forskolin, or isoproterenol, PKB phosphorylation at serine 473 and threonine 308, which is crucial for activation of PKB (20), was assessed. As expected, insulin and IGF-1 strongly stimulated phosphorylation of PKB at serine 473 in NIH 3T3 or Rat1 cells (Fig. 2B). In contrast, 8-Br-cAMP, forskolin, and isoproterenol did not significantly alter PKB phosphorylation at serine 473 (Fig. 2B). Similar results were obtained with a threonine 308 phosphorylation-specific antibody (data not shown). PubMed:11035810

Annotations
Experimental Factor Ontology (EFO)
MCF7 cell
NCBI Taxonomy Ids
10116
Uberon
kidney
Cell Ontology (CL)
neutrophil
MeSH
Cytoplasm
Disease Ontology (DO)
cancer
MeSH
Macrophages

p(HGNC:MAPKAP1) increases p(HGNC:AKT1, pmod(Ph, Ser, 473))

Genetic ablation of sin1 abolished Akt-Ser473 phosphorylation and disrupted rictor-mTOR interaction but maintained Thr308 phosphorylation. PubMed:16962653

Annotations
Experimental Factor Ontology (EFO)
U-937 cell
NCBI Taxonomy Ids
9606
Uberon
cardiovascular system endothelium
Cell Ontology (CL)
endothelial cell
MeSH
Cell Membrane
Disease Ontology (DO)
atherosclerosis
MeSH
Muscle, Smooth, Vascular

path(SDIS:"laminar shear stress") increases p(HGNC:AKT1, pmod(Ph, Ser, 473))

In cells under static conditions low levels of Akt (Ser473) and eNOS (Ser1177) phosphorylation were detected and the application of shear stress (12 dynes cm–2, 30 minutes) was associated with the phosphorylation of Akt as well as that of eNOS (Fig. 3B). The Src-family tyrosine kinase inhibitor PP1 (30 μmol l–1) markedly attenuated the phosphorylation of Akt and eNOS while the inactive compound PP3 failed to affect the response to shear stress. Other:16118242

act(p(SFAM:"SRC Family"), ma(kin)) increases p(HGNC:AKT1, pmod(Ph, Ser, 473))

In cells under static conditions low levels of Akt (Ser473) and eNOS (Ser1177) phosphorylation were detected and the application of shear stress (12 dynes cm–2, 30 minutes) was associated with the phosphorylation of Akt as well as that of eNOS (Fig. 3B). The Src-family tyrosine kinase inhibitor PP1 (30 μmol l–1) markedly attenuated the phosphorylation of Akt and eNOS while the inactive compound PP3 failed to affect the response to shear stress. Other:16118242

act(p(HGNC:ILK), ma(kin)) directlyIncreases p(HGNC:AKT1, pmod(Ph, Ser, 473))

Activation of PKB alpha and beta is then achieved at the plasma membrane by phosphorylation of Thr308/309 in the A-loop of the kinase domain and Ser473/474 in the carboxy-terminal regulatory region, respectively. The upstream kinase that phosphorylates PKB on Thr308, termed PI-dependent protein kinase-1, has been identified and extensively characterised. A candidate for the Ser473/474 kinase, termed the integrin-linked kinase, has been identified recently. PubMed:10454216

Appears in Networks:

p(HGNC:ILK) increases p(HGNC:AKT1, pmod(Ph, Ser, 473))

Knock-down of ILK by small, interfering RNA (siRNA) attenuated Akt phosphorylation in response to ligation of beta1 integrin by collagen or activating antibody and enhanced fibroblast apoptosis in response to collagen contraction. Kinase dead ILK attenuated Akt phosphorylation and enhanced fibroblast apoptosis, whereas hyperactive and wild type ILK augmented Akt phosphorylation and protected fibroblasts from apoptosis. PubMed:15905178

Appears in Networks:

act(p(MGI:Ilk), ma(kin)) directlyIncreases p(HGNC:AKT1, pmod(Ph, Ser, 473))

Activation of PKB alpha and beta is then achieved at the plasma membrane by phosphorylation of Thr308/309 in the A-loop of the kinase domain and Ser473/474 in the carboxy-terminal regulatory region, respectively. The upstream kinase that phosphorylates PKB on Thr308, termed PI-dependent protein kinase-1, has been identified and extensively characterised. A candidate for the Ser473/474 kinase, termed the integrin-linked kinase, has been identified recently. PubMed:10454216

Appears in Networks:

p(MGI:Ilk) increases p(HGNC:AKT1, pmod(Ph, Ser, 473))

Knock-down of ILK by small, interfering RNA (siRNA) attenuated Akt phosphorylation in response to ligation of beta1 integrin by collagen or activating antibody and enhanced fibroblast apoptosis in response to collagen contraction. Kinase dead ILK attenuated Akt phosphorylation and enhanced fibroblast apoptosis, whereas hyperactive and wild type ILK augmented Akt phosphorylation and protected fibroblasts from apoptosis. PubMed:15905178

Appears in Networks:

act(p(RGD:Ilk), ma(kin)) directlyIncreases p(HGNC:AKT1, pmod(Ph, Ser, 473))

Activation of PKB alpha and beta is then achieved at the plasma membrane by phosphorylation of Thr308/309 in the A-loop of the kinase domain and Ser473/474 in the carboxy-terminal regulatory region, respectively. The upstream kinase that phosphorylates PKB on Thr308, termed PI-dependent protein kinase-1, has been identified and extensively characterised. A candidate for the Ser473/474 kinase, termed the integrin-linked kinase, has been identified recently. PubMed:10454216

Appears in Networks:

p(RGD:Ilk) increases p(HGNC:AKT1, pmod(Ph, Ser, 473))

Knock-down of ILK by small, interfering RNA (siRNA) attenuated Akt phosphorylation in response to ligation of beta1 integrin by collagen or activating antibody and enhanced fibroblast apoptosis in response to collagen contraction. Kinase dead ILK attenuated Akt phosphorylation and enhanced fibroblast apoptosis, whereas hyperactive and wild type ILK augmented Akt phosphorylation and protected fibroblasts from apoptosis. PubMed:15905178

Appears in Networks:

p(HGNC:IGF1) increases p(HGNC:AKT1, pmod(Ph, Ser, 473))

We measured phosphorylation of IGF-1R at Tyr 1135/1136 (anti-phospho IGF-1R antibody (Supplementary Fig. 1) that also detects phosphorylation of the insulin receptor(InR)), Akt at Thr 308 and Ser 473, MAPK at Thr202/Tyr204, and S6 at Ser 235/236 and Ser 240/244 (n = 3 cultures, all time points). PubMed:27561791

act(p(HGNC:MTOR), ma(kin)) decreases p(HGNC:AKT1, pmod(Ph, Ser, 473))

Furthermore, we show that inhibition of mTOR by rapamycin induces the activation of Akt as shown by increased Akt phosphorylation at Ser(473) and the inhibition of 6-TG-induced apoptosis and cell death. Activated Akt is a well-known inhibitor of autophagy. PubMed:18381446

a(MESHC:efipladib) decreases act(p(HGNC:AKT1, pmod(Ph, Ser, 473)), ma(kin))

In contrast, silencing of cPLA2α with siRNA or inhibition with Efipladib decreased basal and EGF-stimulated AKT phosphorylation and proliferation in HT-29. Treating animals transplanted with DLD-1 with Efipladib (10 mg/kg, i.p. daily) over 14 days reduced xenograft growth by >90% with a concomitant decrease in AKT phosphorylation. In human CRC tissue, cPLA2α expression and phosphorylation were increased in 63% (77/120) compared with adjacent normal mucosa determined by immunohistochemistry. PubMed:25365190

Annotations
NCBI Taxonomy Ids
9606
Experimental Factor Ontology (EFO)
HT-29
Disease Ontology (DO)
colorectal cancer
MeSH
Rectal Neoplasms

path(MESHD:"Colorectal Neoplasms") association act(p(HGNC:AKT1, pmod(Ph, Ser, 473)), ma(kin))

A constitutive activation of protein kinase B (AKT) in a hyper-phosphorylated status at Ser473 is one of the hallmarks of anti-EGFR therapy-resistant colorectal cancer (CRC). PubMed:25365190

Annotations
NCBI Taxonomy Ids
9606
Experimental Factor Ontology (EFO)
COLO 205 cell
Experimental Factor Ontology (EFO)
HT-29
Disease Ontology (DO)
colorectal cancer
MeSH
Rectal Neoplasms

p(HGNC:KAT5) increases act(p(HGNC:AKT1, pmod(Ph, Ser, 473)), ma(kin))

The aim of this study was to examine the role of cytosolic phospholipase A2α (cPLA2α) on AKT phosphorylation at Ser473 and cell proliferation in CRC cells with mutation in phosphoinositide 3-kinase (PI3K). AKT phosphorylation at Ser473 was resistant to EGF stimulation in CRC cell lines of DLD-1 (PIK3CAE545K mutation) and HT-29 (PIK3CAP499T mutation). Over-expression of cPLA2α by stable transfection increased basal and EGF-stimulated AKT phosphorylation and proliferation in DLD-1 cells. PubMed:25365190

Annotations
NCBI Taxonomy Ids
9606
Experimental Factor Ontology (EFO)
COLO 205 cell
Experimental Factor Ontology (EFO)
HT-29
Disease Ontology (DO)
colorectal cancer
MeSH
Rectal Neoplasms

deg(p(HGNC:KAT5)) decreases act(p(HGNC:AKT1, pmod(Ph, Ser, 473)), ma(kin))

In contrast, silencing of cPLA2α with siRNA or inhibition with Efipladib decreased basal and EGF-stimulated AKT phosphorylation and proliferation in HT-29. Treating animals transplanted with DLD-1 with Efipladib (10 mg/kg, i.p. daily) over 14 days reduced xenograft growth by >90% with a concomitant decrease in AKT phosphorylation. In human CRC tissue, cPLA2α expression and phosphorylation were increased in 63% (77/120) compared with adjacent normal mucosa determined by immunohistochemistry. PubMed:25365190

Annotations
NCBI Taxonomy Ids
9606
Experimental Factor Ontology (EFO)
HT-29
Disease Ontology (DO)
colorectal cancer
MeSH
Rectal Neoplasms

a(MESHC:efipladib) decreases act(p(HGNC:AKT1, pmod(Ph, Ser, 473)), ma(kin))

In contrast, silencing of cPLA2α with siRNA or inhibition with Efipladib decreased basal and EGF-stimulated AKT phosphorylation and proliferation in HT-29. Treating animals transplanted with DLD-1 with Efipladib (10 mg/kg, i.p. daily) over 14 days reduced xenograft growth by >90% with a concomitant decrease in AKT phosphorylation. In human CRC tissue, cPLA2α expression and phosphorylation were increased in 63% (77/120) compared with adjacent normal mucosa determined by immunohistochemistry. PubMed:25365190

Annotations
MeSH
Microtubules
Experimental Factor Ontology (EFO)
HT-29
MeSH
Rectal Neoplasms
Evidence and Conclusion Ontology
immunohistochemistry
MeSH
Plasma
NCBI Taxonomy Names
Mus musculus
Disease Ontology (DO)
colorectal cancer
NCBI Taxonomy Ids
9606

p(HGNC:KAT5) increases act(p(HGNC:AKT1, pmod(Ph, Ser, 473)), ma(kin))

The aim of this study was to examine the role of cytosolic phospholipase A2α (cPLA2α) on AKT phosphorylation at Ser473 and cell proliferation in CRC cells with mutation in phosphoinositide 3-kinase (PI3K). AKT phosphorylation at Ser473 was resistant to EGF stimulation in CRC cell lines of DLD-1 (PIK3CAE545K mutation) and HT-29 (PIK3CAP499T mutation). Over-expression of cPLA2α by stable transfection increased basal and EGF-stimulated AKT phosphorylation and proliferation in DLD-1 cells. PubMed:25365190

Annotations
MeSH
Microtubules
Experimental Factor Ontology (EFO)
COLO 205 cell
Experimental Factor Ontology (EFO)
HT-29
MeSH
Rectal Neoplasms
Evidence and Conclusion Ontology
immunohistochemistry
MeSH
Plasma
NCBI Taxonomy Names
Mus musculus
Disease Ontology (DO)
colorectal cancer
NCBI Taxonomy Ids
9606

deg(p(HGNC:KAT5)) decreases act(p(HGNC:AKT1, pmod(Ph, Ser, 473)), ma(kin))

In contrast, silencing of cPLA2α with siRNA or inhibition with Efipladib decreased basal and EGF-stimulated AKT phosphorylation and proliferation in HT-29. Treating animals transplanted with DLD-1 with Efipladib (10 mg/kg, i.p. daily) over 14 days reduced xenograft growth by >90% with a concomitant decrease in AKT phosphorylation. In human CRC tissue, cPLA2α expression and phosphorylation were increased in 63% (77/120) compared with adjacent normal mucosa determined by immunohistochemistry. PubMed:25365190

Annotations
MeSH
Microtubules
Experimental Factor Ontology (EFO)
HT-29
MeSH
Rectal Neoplasms
Evidence and Conclusion Ontology
immunohistochemistry
MeSH
Plasma
NCBI Taxonomy Names
Mus musculus
Disease Ontology (DO)
colorectal cancer
NCBI Taxonomy Ids
9606

path(MESHD:"Colorectal Neoplasms") association act(p(HGNC:AKT1, pmod(Ph, Ser, 473)), ma(kin))

A constitutive activation of protein kinase B (AKT) in a hyper-phosphorylated status at Ser473 is one of the hallmarks of anti-EGFR therapy-resistant colorectal cancer (CRC). PubMed:25365190

Annotations
MeSH
Microtubules
Experimental Factor Ontology (EFO)
COLO 205 cell
Experimental Factor Ontology (EFO)
HT-29
MeSH
Rectal Neoplasms
Evidence and Conclusion Ontology
immunohistochemistry
MeSH
Plasma
NCBI Taxonomy Names
Mus musculus
Disease Ontology (DO)
colorectal cancer
NCBI Taxonomy Ids
9606

act(p(HGNC:MTOR), ma(kin)) decreases p(HGNC:AKT1, pmod(Ph, Ser, 473))

Furthermore, we show that inhibition of mTOR by rapamycin induces the activation of Akt as shown by increased Akt phosphorylation at Ser(473) and the inhibition of 6-TG-induced apoptosis and cell death. Activated Akt is a well-known inhibitor of autophagy. PubMed:18381446

a(MESHC:efipladib) decreases act(p(HGNC:AKT1, pmod(Ph, Ser, 473)), ma(kin))

In contrast, silencing of cPLA2α with siRNA or inhibition with Efipladib decreased basal and EGF-stimulated AKT phosphorylation and proliferation in HT-29. Treating animals transplanted with DLD-1 with Efipladib (10 mg/kg, i.p. daily) over 14 days reduced xenograft growth by >90% with a concomitant decrease in AKT phosphorylation. In human CRC tissue, cPLA2α expression and phosphorylation were increased in 63% (77/120) compared with adjacent normal mucosa determined by immunohistochemistry. PubMed:25365190

path(MESHD:"Colorectal Neoplasms") association act(p(HGNC:AKT1, pmod(Ph, Ser, 473)), ma(kin))

A constitutive activation of protein kinase B (AKT) in a hyper-phosphorylated status at Ser473 is one of the hallmarks of anti-EGFR therapy-resistant colorectal cancer (CRC). PubMed:25365190

p(HGNC:KAT5) increases act(p(HGNC:AKT1, pmod(Ph, Ser, 473)), ma(kin))

The aim of this study was to examine the role of cytosolic phospholipase A2α (cPLA2α) on AKT phosphorylation at Ser473 and cell proliferation in CRC cells with mutation in phosphoinositide 3-kinase (PI3K). AKT phosphorylation at Ser473 was resistant to EGF stimulation in CRC cell lines of DLD-1 (PIK3CAE545K mutation) and HT-29 (PIK3CAP499T mutation). Over-expression of cPLA2α by stable transfection increased basal and EGF-stimulated AKT phosphorylation and proliferation in DLD-1 cells. PubMed:25365190

deg(p(HGNC:KAT5)) decreases act(p(HGNC:AKT1, pmod(Ph, Ser, 473)), ma(kin))

In contrast, silencing of cPLA2α with siRNA or inhibition with Efipladib decreased basal and EGF-stimulated AKT phosphorylation and proliferation in HT-29. Treating animals transplanted with DLD-1 with Efipladib (10 mg/kg, i.p. daily) over 14 days reduced xenograft growth by >90% with a concomitant decrease in AKT phosphorylation. In human CRC tissue, cPLA2α expression and phosphorylation were increased in 63% (77/120) compared with adjacent normal mucosa determined by immunohistochemistry. PubMed:25365190

act(p(HGNC:MTOR), ma(kin)) decreases p(HGNC:AKT1, pmod(Ph, Ser, 473))

Furthermore, we show that inhibition of mTOR by rapamycin induces the activation of Akt as shown by increased Akt phosphorylation at Ser(473) and the inhibition of 6-TG-induced apoptosis and cell death. Activated Akt is a well-known inhibitor of autophagy. PubMed:18381446

Appears in Networks:
Annotations
MeSH
Cytoplasm
MeSH
Condylomata Acuminata
Evidence and Conclusion Ontology
immunohistochemistry
MeSH
Plasma
NCBI Taxonomy Names
Mus musculus
NCBI Taxonomy Ids
9606

bp(MESHPP:"Drug Resistance") association act(p(HGNC:AKT1, pmod(Ph, Ser, 473)), ma(kin))

A constitutive activation of protein kinase B (AKT) in a hyper-phosphorylated status at Ser473 is one of the hallmarks of anti-EGFR therapy-resistant colorectal cancer (CRC). PubMed:25365190

Annotations
Experimental Factor Ontology (EFO)
COLO 205 cell
Experimental Factor Ontology (EFO)
HT-29
MeSH
Intracellular Space
MeSH
Rectal Neoplasms
MeSH
Mucus
NCBI Taxonomy Names
Crataegus azarolus
Disease Ontology (DO)
colorectal cancer
Uberon
intestinal epithelium
Cell Ontology (CL)
stem cell
NCBI Taxonomy Ids
9606

path(MESHD:"Colorectal Neoplasms") association act(p(HGNC:AKT1, pmod(Ph, Ser, 473)), ma(kin))

A constitutive activation of protein kinase B (AKT) in a hyper-phosphorylated status at Ser473 is one of the hallmarks of anti-EGFR therapy-resistant colorectal cancer (CRC). PubMed:25365190

Annotations
Experimental Factor Ontology (EFO)
COLO 205 cell
Experimental Factor Ontology (EFO)
HT-29
MeSH
Intracellular Space
MeSH
Rectal Neoplasms
MeSH
Mucus
NCBI Taxonomy Names
Crataegus azarolus
Disease Ontology (DO)
colorectal cancer
Uberon
intestinal epithelium
Cell Ontology (CL)
stem cell
NCBI Taxonomy Ids
9606

a(MESHC:efipladib) decreases act(p(HGNC:AKT1, pmod(Ph, Ser, 473)), ma(kin))

In contrast, silencing of cPLA2α with siRNA or inhibition with Efipladib decreased basal and EGF-stimulated AKT phosphorylation and proliferation in HT-29. Treating animals transplanted with DLD-1 with Efipladib (10 mg/kg, i.p. daily) over 14 days reduced xenograft growth by >90% with a concomitant decrease in AKT phosphorylation. In human CRC tissue, cPLA2α expression and phosphorylation were increased in 63% (77/120) compared with adjacent normal mucosa determined by immunohistochemistry. PubMed:25365190

Annotations
Experimental Factor Ontology (EFO)
HT-29
MeSH
Intracellular Space
MeSH
Rectal Neoplasms
MeSH
Mucus
NCBI Taxonomy Names
Crataegus azarolus
Disease Ontology (DO)
colorectal cancer
Uberon
intestinal epithelium
Cell Ontology (CL)
stem cell
NCBI Taxonomy Ids
9606

act(p(HGNC:MTOR), ma(kin)) decreases p(HGNC:AKT1, pmod(Ph, Ser, 473))

Furthermore, we show that inhibition of mTOR by rapamycin induces the activation of Akt as shown by increased Akt phosphorylation at Ser(473) and the inhibition of 6-TG-induced apoptosis and cell death. Activated Akt is a well-known inhibitor of autophagy. PubMed:18381446

Annotations
Experimental Factor Ontology (EFO)
NCI-H1299 cell
MeSH
Cytoplasm
MeSH
Lung Neoplasms
MeSH
Lung
Cell Ontology (CL)
stem cell
NCBI Taxonomy Ids
9606

p(HGNC:KAT5) increases act(p(HGNC:AKT1, pmod(Ph, Ser, 473)), ma(kin))

The aim of this study was to examine the role of cytosolic phospholipase A2α (cPLA2α) on AKT phosphorylation at Ser473 and cell proliferation in CRC cells with mutation in phosphoinositide 3-kinase (PI3K). AKT phosphorylation at Ser473 was resistant to EGF stimulation in CRC cell lines of DLD-1 (PIK3CAE545K mutation) and HT-29 (PIK3CAP499T mutation). Over-expression of cPLA2α by stable transfection increased basal and EGF-stimulated AKT phosphorylation and proliferation in DLD-1 cells. PubMed:25365190

Annotations
Experimental Factor Ontology (EFO)
COLO 205 cell
Experimental Factor Ontology (EFO)
HT-29
MeSH
Intracellular Space
MeSH
Rectal Neoplasms
MeSH
Mucus
NCBI Taxonomy Names
Crataegus azarolus
Disease Ontology (DO)
colorectal cancer
Uberon
intestinal epithelium
Cell Ontology (CL)
stem cell
NCBI Taxonomy Ids
9606

deg(p(HGNC:KAT5)) decreases act(p(HGNC:AKT1, pmod(Ph, Ser, 473)), ma(kin))

In contrast, silencing of cPLA2α with siRNA or inhibition with Efipladib decreased basal and EGF-stimulated AKT phosphorylation and proliferation in HT-29. Treating animals transplanted with DLD-1 with Efipladib (10 mg/kg, i.p. daily) over 14 days reduced xenograft growth by >90% with a concomitant decrease in AKT phosphorylation. In human CRC tissue, cPLA2α expression and phosphorylation were increased in 63% (77/120) compared with adjacent normal mucosa determined by immunohistochemistry. PubMed:25365190

Annotations
Experimental Factor Ontology (EFO)
HT-29
MeSH
Intracellular Space
MeSH
Rectal Neoplasms
MeSH
Mucus
NCBI Taxonomy Names
Crataegus azarolus
Disease Ontology (DO)
colorectal cancer
Uberon
intestinal epithelium
Cell Ontology (CL)
stem cell
NCBI Taxonomy Ids
9606

p(HGNC:PIK3CA, var(p.Glu545Lys)) association act(p(HGNC:AKT1, pmod(Ph, Ser, 473)), ma(kin))

The aim of this study was to examine the role of cytosolic phospholipase A2α (cPLA2α) on AKT phosphorylation at Ser473 and cell proliferation in CRC cells with mutation in phosphoinositide 3-kinase (PI3K). AKT phosphorylation at Ser473 was resistant to EGF stimulation in CRC cell lines of DLD-1 (PIK3CAE545K mutation) and HT-29 (PIK3CAP499T mutation). Over-expression of cPLA2α by stable transfection increased basal and EGF-stimulated AKT phosphorylation and proliferation in DLD-1 cells. PubMed:25365190

Annotations
Experimental Factor Ontology (EFO)
COLO 205 cell
Experimental Factor Ontology (EFO)
HT-29
MeSH
Intracellular Space
MeSH
Rectal Neoplasms
MeSH
Mucus
NCBI Taxonomy Names
Crataegus azarolus
Disease Ontology (DO)
colorectal cancer
Uberon
intestinal epithelium
Cell Ontology (CL)
stem cell
NCBI Taxonomy Ids
9606

a(SCHEM:"LY 294002") decreases p(HGNC:AKT1, pmod(Ph, Ser, 473))

Moreover, both ZJW and a PI3K specific inhibitor (LY294002) suppressed phosphorylation of Akt (Ser473) and NF-κB, which is necessary in the activation of the PI3K/Akt/NF-κB pathway. PubMed:25085593

Annotations
Experimental Factor Ontology (EFO)
COLO205
MeSH
Chromatin
MeSH
Colorectal Neoplasms
Evidence and Conclusion Ontology
western blot
MeSH
Colon
NCBI Taxonomy Names
Homo sapiens
Disease Ontology (DO)
colorectal cancer
Uberon
intestinal epithelium
Cell Ontology (CL)
stem cell
NCBI Taxonomy Ids
10090

p(HGNC:PIK3CA, var(p.Pro499Thr)) association act(p(HGNC:AKT1, pmod(Ph, Ser, 473)), ma(kin))

The aim of this study was to examine the role of cytosolic phospholipase A2α (cPLA2α) on AKT phosphorylation at Ser473 and cell proliferation in CRC cells with mutation in phosphoinositide 3-kinase (PI3K). AKT phosphorylation at Ser473 was resistant to EGF stimulation in CRC cell lines of DLD-1 (PIK3CAE545K mutation) and HT-29 (PIK3CAP499T mutation). Over-expression of cPLA2α by stable transfection increased basal and EGF-stimulated AKT phosphorylation and proliferation in DLD-1 cells. PubMed:25365190

Annotations
Experimental Factor Ontology (EFO)
COLO 205 cell
Experimental Factor Ontology (EFO)
HT-29
MeSH
Intracellular Space
MeSH
Rectal Neoplasms
MeSH
Mucus
NCBI Taxonomy Names
Crataegus azarolus
Disease Ontology (DO)
colorectal cancer
Uberon
intestinal epithelium
Cell Ontology (CL)
stem cell
NCBI Taxonomy Ids
9606

bp(MESHPP:"Drug Resistance") association act(p(HGNC:AKT1, pmod(Ph, Ser, 473)), ma(kin))

A constitutive activation of protein kinase B (AKT) in a hyper-phosphorylated status at Ser473 is one of the hallmarks of anti-EGFR therapy-resistant colorectal cancer (CRC). PubMed:25365190

act(p(HGNC:MTOR), ma(kin)) decreases p(HGNC:AKT1, pmod(Ph, Ser, 473))

Furthermore, we show that inhibition of mTOR by rapamycin induces the activation of Akt as shown by increased Akt phosphorylation at Ser(473) and the inhibition of 6-TG-induced apoptosis and cell death. Activated Akt is a well-known inhibitor of autophagy. PubMed:18381446

p(HGNC:PIK3CA, var(p.Glu545Lys)) association act(p(HGNC:AKT1, pmod(Ph, Ser, 473)), ma(kin))

The aim of this study was to examine the role of cytosolic phospholipase A2α (cPLA2α) on AKT phosphorylation at Ser473 and cell proliferation in CRC cells with mutation in phosphoinositide 3-kinase (PI3K). AKT phosphorylation at Ser473 was resistant to EGF stimulation in CRC cell lines of DLD-1 (PIK3CAE545K mutation) and HT-29 (PIK3CAP499T mutation). Over-expression of cPLA2α by stable transfection increased basal and EGF-stimulated AKT phosphorylation and proliferation in DLD-1 cells. PubMed:25365190

a(SCHEM:"LY 294002") decreases p(HGNC:AKT1, pmod(Ph, Ser, 473))

Moreover, both ZJW and a PI3K specific inhibitor (LY294002) suppressed phosphorylation of Akt (Ser473) and NF-κB, which is necessary in the activation of the PI3K/Akt/NF-κB pathway. PubMed:25085593

p(HGNC:PIK3CA, var(p.Pro499Thr)) association act(p(HGNC:AKT1, pmod(Ph, Ser, 473)), ma(kin))

The aim of this study was to examine the role of cytosolic phospholipase A2α (cPLA2α) on AKT phosphorylation at Ser473 and cell proliferation in CRC cells with mutation in phosphoinositide 3-kinase (PI3K). AKT phosphorylation at Ser473 was resistant to EGF stimulation in CRC cell lines of DLD-1 (PIK3CAE545K mutation) and HT-29 (PIK3CAP499T mutation). Over-expression of cPLA2α by stable transfection increased basal and EGF-stimulated AKT phosphorylation and proliferation in DLD-1 cells. PubMed:25365190

complex(GOCC:"phosphatidylinositol 3-kinase complex") directlyIncreases p(HGNC:AKT1, pmod(Ph, Ser, 473))

Recent research has indicated several potential inhibitors of Akt activity. PI3-kinase inhibitor, LY294002 or wortmannin, could reduce Akt activity and prevent phosphorylation of Akt and increase DNA damage after focal cerebral ischemia and global ischemia. PubMed:22643085

Appears in Networks:

Out-Edges 88

p(HGNC:AKT1, pmod(Ph, Ser, 473)) directlyIncreases act(p(HGNC:AKT1), ma(kin))

In this paper, we present a comprehensive pathway map of EGFR signaling and other related pathways. Other:Mol Sys Biol 2005 May msb4100014

Annotations
Experimental Factor Ontology (EFO)
3T3-L1 cell
NCBI Taxonomy Ids
9606
Uberon
liver
Cell Ontology (CL)
fibroblast
MeSH
Cytoplasm
Disease Ontology (DO)
estrogen-receptor positive breast cancer

p(HGNC:AKT1, pmod(Ph, Ser, 473)) directlyIncreases act(p(HGNC:AKT1), ma(kin))

Activation of PKB alpha and beta is then achieved at the plasma membrane by phosphorylation of Thr308/309 in the A-loop of the kinase domain and Ser473/474 in the carboxy-terminal regulatory region, respectively. The upstream kinase that phosphorylates PKB on Thr308, termed PI-dependent protein kinase-1, has been identified and extensively characterised. A candidate for the Ser473/474 kinase, termed the integrin-linked kinase, has been identified recently. PubMed:10454216

Annotations
Experimental Factor Ontology (EFO)
U-937 cell
NCBI Taxonomy Ids
9606
Uberon
skeletal muscle tissue
Cell Ontology (CL)
macrophage
MeSH
Cytoplasm
Disease Ontology (DO)
leukemia

p(HGNC:AKT1, pmod(Ph, Ser, 473)) directlyIncreases act(p(HGNC:AKT1), ma(kin))

As shown in Fig. 2 B, subconfluent HeLa cultures have relatively low levels of active PKB, as detected by antibodies specifically recognizing PKB phosphorylated on serine 473. Phosphorylation of PKB is fully inhibitable by treatment with the specific PI 3-kinase inhibitor LY294002. Sparse cultures have barely detectable levels of phosphorylated PKB; however, dense cultures have much more activated PKB, whereas the total levels of PKB protein remain constant under all conditions examined. PubMed:11535620

Annotations
Experimental Factor Ontology (EFO)
HeLa cell
NCBI Taxonomy Ids
9606
Uberon
cardiovascular system endothelium
Cell Ontology (CL)
leukocyte
MeSH
Cytoplasm
Disease Ontology (DO)
multiple myeloma

p(HGNC:AKT1, pmod(Ph, Ser, 473)) directlyIncreases act(p(HGNC:AKT1), ma(kin))

three isoforms, AKT1 (PKBalpha), AKT2 (PKBbeta) and AKT3 (PKBgamma) they all contain a central kinase domain with an activation-loop phosphorylation site, Thr308, and a conserved, regulatory C-terminal phosphorylation site, Ser473 PubMed:12044776

Annotations
Experimental Factor Ontology (EFO)
HUVEC cell line
NCBI Taxonomy Ids
9606
Uberon
blood plasma
Cell Ontology (CL)
T cell
MeSH
Cell Membrane
Disease Ontology (DO)
sarcoma

p(HGNC:AKT1, pmod(Ph, Ser, 473)) directlyIncreases act(p(HGNC:AKT1), ma(kin))

Overexpressed IRS-3 as well as IRS-1 enhanced phosphoinositide (PI) 3-kinase activity in response to insulin and increased phosphorylation of protein kinase B (PKB) at S473 and phosphorylation of one of the members of the forkhead transcription factor FKHRL1 on T32 in both insulin-untreated and -treated states. PubMed:12504093

Annotations
Experimental Factor Ontology (EFO)
NIH-3T3 cell
NCBI Taxonomy Ids
9606
Uberon
heart
Cell Ontology (CL)
hepatocyte
MeSH
Cell Membrane
Disease Ontology (DO)
atherosclerosis

p(HGNC:AKT1, pmod(Ph, Ser, 473)) directlyIncreases act(p(HGNC:AKT1), ma(kin))

Fig. 1. Insulin-like growth factor 1 (IGF-1)-mediated signaling pathways relevant to hypertrophy. Binding of IGF-1 activates the IGF-1 receptor (purple), which then recruits insulin-receptor substrate (IRS-1). This leads to the activation of two signaling pathways: the Ras-Raf-MEK-ERK pathway and the phosphatidylinositol 3-kinase (PI3K)- Akt pathway. The PI3K-Akt pathway recapitulates hypertrophy caused by IGF-1 stimulation. Akt1 activity can be modulated either by directly controlling its phosphorylation state or by altering the levels of the lipid that it binds at the cell membrane, phosphatidylinositol (3,4,5)-trisphosphate [PtdIns(3,4,5)P3] (orange). Signaling molecules that have been shown to have a negative effect on hypertrophy are colored red, and proteins whose activation induces hypertrophy are shown in green. Proteins that have not been assayed for their role in hypertrophy are shown in blue. Abbreviations: eIF-2B, eukaryotic translation initiation factor 2B; ERK, extracellular-signal-regulated kinase; GSK3b, glycogen-synthase kinase 3b; mTOR, mammalian target of rapamycin; p70S6K, p70 S6 kinase; PDK, phosphoinositide-dependent protein kinase; PtdIns(3,4)P2, phosphatidylinositol (3,4)-bisphosphate; PtdIns(4,5)P2, phosphatidylinositol (4,5)-bisphosphate; PHAS-1, phosphorylated heat- and acid-stable protein 1; PP2A, protein phosphatase 2A; PTEN, phosphatase and tensin homologous on chromosome 10; SHIP2, SH2-domain-containing inositol phosphatase; Tsc1/2, tuberous sclerosis complex 1 and 2. Modified from Ref. [87]. Akt1 activity can be modulated either by directly controlling its phosphorylation state or by altering the levels of the lipid that it binds at the cell membrane, PtdIns(3,4,5)P3 [22] (Fig. 1). Akt1 activity depends on phosphorylation at two sites: Ser473 and Thr309 [29]. PubMed:12928036

Annotations
Experimental Factor Ontology (EFO)
C3H/10T1/2, Clone 8 cell
NCBI Taxonomy Ids
9606
Uberon
heart
Cell Ontology (CL)
cardiac muscle cell
MeSH
Cell Nucleus
Disease Ontology (DO)
hematologic cancer

p(HGNC:AKT1, pmod(Ph, Ser, 473)) directlyIncreases act(p(HGNC:AKT1), ma(kin))

Stimulation of platelets with a PAR1-activating peptide (SFLLRN), PAR4-activating peptide (AYPGKF), and thrombin resulted in Thr308 and Ser473 phosphorylation of Akt, which results in its activation. PubMed:14623889

Annotations
Experimental Factor Ontology (EFO)
Hep 3B cell
NCBI Taxonomy Ids
9606
Uberon
blood vessel smooth muscle
Cell Ontology (CL)
platelet
MeSH
Cell Membrane
Disease Ontology (DO)
lung cancer

p(HGNC:AKT1, pmod(Ph, Ser, 473)) directlyIncreases act(p(HGNC:AKT1), ma(kin))

Furthermore, serum starvation-induced apoptosis caused a twofold increase in caspase 3 activity in C1-TEN-overexpressing cells vs. mock cells. In addition, C1-TEN-overexpressing cells showed a markedly reduced phosphorylation of Akt/PKB kinase and its substrate GSK3, as well as reduced Akt enzymatic activity. Equal amounts of total cell lysates were subjected to 10% SDSPAGE. The membrane was then probed with polyclonal antibody against GSK3 specifically phosphorylated at Ser21/9 (pGSK3?/?, CST), after which the membrane was stripped (stripping buffer, Pierce) and reprobed with polyclonal anti-total Akt antibody (CST). and Western blotting for detection of either Akt kinase specifically phosphorylated at Ser473 (pAkt) or both 42 and 44 kDa isoforms of phosphorylated ERK (pERK) using specific antibodies (Santa Cruz Biotechnology, Santa Cruz, CA). PubMed:15817639

Annotations
Experimental Factor Ontology (EFO)
Caco-2 cell
NCBI Taxonomy Ids
9606
Uberon
lung
Cell Ontology (CL)
endothelial cell
MeSH
Cell Membrane
Disease Ontology (DO)
non-small cell lung carcinoma
MeSH
Sputum
MeSH
Head and Neck Neoplasms

p(HGNC:AKT1, pmod(Ph, Ser, 473)) directlyIncreases act(p(HGNC:AKT1), ma(kin))

Upon stimulation with insulin, AKT is recruited to cellular membranes by binding of its amino terminal pleckstrin (PH) domain to membrane bound phosphatidylinositol 3,4,5, trisphosphate (PIP3) [3]. The membrane bound form of AKT then becomes phosphorylated on two regulatory residues, a threonine within the activation loop (Thr308 in AKT1,Thr309 in AKT2, Thr305 in AKT3) and a serine in the C-terminus of the enzyme (Ser473 in AKT1,Ser474 in AKT2, Ser472 in AKT3), and both phosphorylations are considered to be required for AKT to reach maximum kinase activity [1]. The kinase responsible for phosphorylation of Thr308/309/305 has been identified as phosphoinositide-dependent kinase 1 (PDK1) [3]. PubMed:15890450

Annotations
Experimental Factor Ontology (EFO)
MCF7 cell
NCBI Taxonomy Ids
9606
Uberon
adipose tissue
Cell Ontology (CL)
keratinocyte
MeSH
Cell Membrane
Disease Ontology (DO)
multiple myeloma
MeSH
Sputum
MeSH
Head and Neck Neoplasms

p(HGNC:AKT1, pmod(Ph, Ser, 473)) directlyIncreases act(p(HGNC:AKT1), ma(kin))

After PIP3 binding, Akt1 is activated by phosphorylation on two critical residues, namely threonine %308 (T308) and serine 473 (S473); similar activation residues (S472 and S474, %respectively) are highly conserved in Akt2 and Akt3 Phosphoinositol-3-phosphate (PIP3) is a product of phosphoinositol 3-kinase enzymatic activity and has been shown to be a prerequisite lipid modulator of Akt activity Akt activity can be regulated by the PTEN tumour suppressor gene, which negatively regulates PIP3 levels PIP3 has been described as a downstream component of a wide range of receptors, including the c-Met receptor [5], the epidermal growth factor receptor family [6], fibroblast growth factor receptor [7], insulin growth factor receptor [8] and platelet-derived growth factor receptor PubMed:15987444

Annotations
Experimental Factor Ontology (EFO)
NIH-3T3 cell
NCBI Taxonomy Ids
9606
Uberon
pancreas
Cell Ontology (CL)
neuron
MeSH
Cell Nucleus
Disease Ontology (DO)
colon cancer
MeSH
Sputum
MeSH
Head and Neck Neoplasms

p(HGNC:AKT1, pmod(Ph, Ser, 473)) directlyIncreases act(p(HGNC:AKT1), ma(kin))

IL-4 induces PI-3K activity, as shown by Western blotting analysis, demonstrating the specific phosphorylation of PKB, a downstream substrate of PI-3K, at residues Ser473 and Thr308. PubMed:17200144

Annotations
Experimental Factor Ontology (EFO)
HUVEC cell line
NCBI Taxonomy Ids
9606
Uberon
adipose tissue
Cell Ontology (CL)
CD8-positive, alpha-beta regulatory T cell
MeSH
Cell Nucleus
Disease Ontology (DO)
prostate cancer
MeSH
Sputum
MeSH
Head and Neck Neoplasms

p(HGNC:AKT1, pmod(Ph, Ser, 473)) directlyIncreases act(p(HGNC:AKT1), ma(kin))

Akt becomes activated upon phosphorylation of Ser473 and Thr308. In the absence of insulin, dexamethasone reduced Ser473 phosphorylation by 33% (P < 0.05 vs. no treatment, n = 3). PubMed:17229808

Annotations
Experimental Factor Ontology (EFO)
PANC-1 cell
NCBI Taxonomy Ids
9606
Uberon
colon
Cell Ontology (CL)
nephron tubule epithelial cell
MeSH
Cell Nucleus
Disease Ontology (DO)
prostate cancer
MeSH
Sputum
MeSH
Head and Neck Neoplasms

p(HGNC:AKT1, pmod(Ph, Ser, 473)) directlyIncreases act(p(HGNC:AKT1), ma(kin))

Thrombin induces the activation of platelet serine/threonine kinase Akt. Akt activation is dependent on its phosphorylation at threonine 308 and serine 473. PubMed:17883592

Annotations
Experimental Factor Ontology (EFO)
MDA-MB-231 cell
NCBI Taxonomy Ids
9606
Uberon
adipose tissue
Cell Ontology (CL)
platelet
MeSH
Cell Nucleus
Disease Ontology (DO)
non-small cell lung carcinoma
MeSH
Sputum
MeSH
Head and Neck Neoplasms

p(HGNC:AKT1, pmod(Ph, Ser, 473)) directlyIncreases act(p(HGNC:AKT1), ma(kin))

Furthermore, we show that inhibition of mTOR by rapamycin induces the activation of Akt as shown by increased Akt phosphorylation at Ser(473) and the inhibition of 6-TG-induced apoptosis and cell death. Activated Akt is a well-known inhibitor of autophagy. PubMed:18381446

Annotations
Experimental Factor Ontology (EFO)
NCI-H292 cell
NCBI Taxonomy Ids
9606
Uberon
cardiac ventricle
Cell Ontology (CL)
bronchial epithelial cell
MeSH
Cell Nucleus
Disease Ontology (DO)
leukemia
MeSH
Sputum
MeSH
Head and Neck Neoplasms

p(HGNC:AKT1, pmod(Ph, Ser, 473)) directlyIncreases act(p(HGNC:AKT1), ma(kin))

Phosphorylation at Ser473 in the hydrophobic motif, along with Thr308 in its activation loop, is considered necessary for Akt function. PubMed:20691662

Annotations
Experimental Factor Ontology (EFO)
HeLa cell
NCBI Taxonomy Ids
9606
Uberon
gall bladder
Cell Ontology (CL)
T cell
MeSH
Cell Membrane
Disease Ontology (DO)
glioblastoma multiforme
MeSH
Sputum
MeSH
Head and Neck Neoplasms

p(HGNC:AKT1, pmod(Ph, Ser, 473)) directlyIncreases act(p(HGNC:AKT1), ma(kin))

The impact of IL-8 binding to AAT or HSA on its ability to stimulate Akt Ser473 phosphorylation, a key step in IL-8? mediated neutrophil chemotaxis (27), was explored. Figure 7D shows that IL-8 (1 ng) stimulated adequate Akt phosphorylation after just 10 minutes and that this effect was unaffected by prebinding of IL-8 to HSA (27.5 uM). PubMed:21060150

Annotations
Experimental Factor Ontology (EFO)
HL-60 cell
NCBI Taxonomy Ids
9606
Uberon
peritoneum
Cell Ontology (CL)
neutrophil
MeSH
Cell Membrane
Disease Ontology (DO)
glioblastoma multiforme
MeSH
Sputum
MeSH
Head and Neck Neoplasms

p(HGNC:AKT1, pmod(Ph, Ser, 473)) directlyIncreases act(p(HGNC:AKT1), ma(kin))

In vivo 32P labeling and mutagenesis demonstrated that m/p-PKBalpha activity was due to phosphorylation on Thr308 and Ser473, that are normally induced on PKB following stimulation of the cells with insulin or insulin-like growth factor-1 (IGF-1).... Following activation the kinase detached from the membrane and translocated to the nucleus. PubMed:9395488

Annotations
Experimental Factor Ontology (EFO)
HUVEC cell line
NCBI Taxonomy Ids
9606
Uberon
epithelium
Cell Ontology (CL)
T cell
MeSH
Cell Membrane
Disease Ontology (DO)
B-cell lymphoma
MeSH
Sputum
MeSH
Head and Neck Neoplasms

p(HGNC:AKT1, pmod(Ph, Ser, 473)) directlyIncreases act(p(HGNC:AKT1), ma(kin))

Phosphorylation at Ser473, along with Thr308 of its activation loop, is deemed necessary for Akt function, although the regulatory mechanisms and physiological importance of each phosphorylation site remain to be fully understood. PubMed:16962653

Annotations
Experimental Factor Ontology (EFO)
U-937 cell
NCBI Taxonomy Ids
9606
Uberon
cardiovascular system endothelium
Cell Ontology (CL)
endothelial cell
MeSH
Cell Membrane
Disease Ontology (DO)
atherosclerosis
MeSH
Muscle, Smooth, Vascular

p(HGNC:AKT1, pmod(Ph, Ser, 473)) directlyIncreases act(p(HGNC:AKT1), ma(kin))

Thrombin induces the activation of platelet serine/threonine kinase Akt. Akt activation is dependent on its phosphorylation at threonine 308 and serine 473. PubMed:17883592

p(HGNC:AKT1, pmod(Ph, Ser, 473)) directlyIncreases act(p(HGNC:AKT1), ma(kin))

Fig. 1. Insulin-like growth factor 1 (IGF-1)-mediated signaling pathways relevant to hypertrophy. Binding of IGF-1 activates the IGF-1 receptor (purple), which then recruits insulin-receptor substrate (IRS-1). This leads to the activation of two signaling pathways: the Ras-Raf-MEK-ERK pathway and the phosphatidylinositol 3-kinase (PI3K)- Akt pathway. The PI3K-Akt pathway recapitulates hypertrophy caused by IGF-1 stimulation. Akt1 activity can be modulated either by directly controlling its phosphorylation state or by altering the levels of the lipid that it binds at the cell membrane, phosphatidylinositol (3,4,5)-trisphosphate [PtdIns(3,4,5)P3] (orange). Signaling molecules that have been shown to have a negative effect on hypertrophy are colored red, and proteins whose activation induces hypertrophy are shown in green. Proteins that have not been assayed for their role in hypertrophy are shown in blue. Abbreviations: eIF-2B, eukaryotic translation initiation factor 2B; ERK, extracellular-signal-regulated kinase; GSK3b, glycogen-synthase kinase 3b; mTOR, mammalian target of rapamycin; p70S6K, p70 S6 kinase; PDK, phosphoinositide-dependent protein kinase; PtdIns(3,4)P2, phosphatidylinositol (3,4)-bisphosphate; PtdIns(4,5)P2, phosphatidylinositol (4,5)-bisphosphate; PHAS-1, phosphorylated heat- and acid-stable protein 1; PP2A, protein phosphatase 2A; PTEN, phosphatase and tensin homologous on chromosome 10; SHIP2, SH2-domain-containing inositol phosphatase; Tsc1/2, tuberous sclerosis complex 1 and 2. Modified from Ref. [87]. Akt1 activity can be modulated either by directly controlling its phosphorylation state or by altering the levels of the lipid that it binds at the cell membrane, PtdIns(3,4,5)P3 [22] (Fig. 1). Akt1 activity depends on phosphorylation at two sites: Ser473 and Thr309 [29]. PubMed:12928036

p(HGNC:AKT1, pmod(Ph, Ser, 473)) directlyIncreases act(p(HGNC:AKT1), ma(kin))

Activation of PKB alpha and beta is then achieved at the plasma membrane by phosphorylation of Thr308/309 in the A-loop of the kinase domain and Ser473/474 in the carboxy-terminal regulatory region, respectively. The upstream kinase that phosphorylates PKB on Thr308, termed PI-dependent protein kinase-1, has been identified and extensively characterised. A candidate for the Ser473/474 kinase, termed the integrin-linked kinase, has been identified recently. PubMed:10454216

p(HGNC:AKT1, pmod(Ph, Ser, 473)) directlyIncreases act(p(HGNC:AKT1), ma(kin))

Upon stimulation with insulin, AKT is recruited to cellular membranes by binding of its amino terminal pleckstrin (PH) domain to membrane bound phosphatidylinositol 3,4,5, trisphosphate (PIP3) [3]. The membrane bound form of AKT then becomes phosphorylated on two regulatory residues, a threonine within the activation loop (Thr308 in AKT1,Thr309 in AKT2, Thr305 in AKT3) and a serine in the C-terminus of the enzyme (Ser473 in AKT1,Ser474 in AKT2, Ser472 in AKT3), and both phosphorylations are considered to be required for AKT to reach maximum kinase activity [1]. The kinase responsible for phosphorylation of Thr308/309/305 has been identified as phosphoinositide-dependent kinase 1 (PDK1) [3]. PubMed:15890450

p(HGNC:AKT1, pmod(Ph, Ser, 473)) directlyIncreases act(p(HGNC:AKT1), ma(kin))

The impact of IL-8 binding to AAT or HSA on its ability to stimulate Akt Ser473 phosphorylation, a key step in IL-8? mediated neutrophil chemotaxis (27), was explored. Figure 7D shows that IL-8 (1 ng) stimulated adequate Akt phosphorylation after just 10 minutes and that this effect was unaffected by prebinding of IL-8 to HSA (27.5 uM). PubMed:21060150

p(HGNC:AKT1, pmod(Ph, Ser, 473)) directlyIncreases act(p(HGNC:AKT1), ma(kin))

In vivo 32P labeling and mutagenesis demonstrated that m/p-PKBalpha activity was due to phosphorylation on Thr308 and Ser473, that are normally induced on PKB following stimulation of the cells with insulin or insulin-like growth factor-1 (IGF-1).... Following activation the kinase detached from the membrane and translocated to the nucleus. PubMed:9395488

p(HGNC:AKT1, pmod(Ph, Ser, 473)) directlyIncreases act(p(HGNC:AKT1), ma(kin))

Akt becomes activated upon phosphorylation of Ser473 and Thr308. In the absence of insulin, dexamethasone reduced Ser473 phosphorylation by 33% (P < 0.05 vs. no treatment, n = 3). PubMed:17229808

p(HGNC:AKT1, pmod(Ph, Ser, 473)) directlyIncreases act(p(HGNC:AKT1), ma(kin))

three isoforms, AKT1 (PKBalpha), AKT2 (PKBbeta) and AKT3 (PKBgamma) they all contain a central kinase domain with an activation-loop phosphorylation site, Thr308, and a conserved, regulatory C-terminal phosphorylation site, Ser473 PubMed:12044776

p(HGNC:AKT1, pmod(Ph, Ser, 473)) directlyIncreases act(p(HGNC:AKT1), ma(kin))

Furthermore, we show that inhibition of mTOR by rapamycin induces the activation of Akt as shown by increased Akt phosphorylation at Ser(473) and the inhibition of 6-TG-induced apoptosis and cell death. Activated Akt is a well-known inhibitor of autophagy. PubMed:18381446

p(HGNC:AKT1, pmod(Ph, Ser, 473)) directlyIncreases act(p(HGNC:AKT1), ma(kin))

Stimulation of platelets with a PAR1-activating peptide (SFLLRN), PAR4-activating peptide (AYPGKF), and thrombin resulted in Thr308 and Ser473 phosphorylation of Akt, which results in its activation. PubMed:14623889

p(HGNC:AKT1, pmod(Ph, Ser, 473)) directlyIncreases act(p(HGNC:AKT1), ma(kin))

After PIP3 binding, Akt1 is activated by phosphorylation on two critical residues, namely threonine %308 (T308) and serine 473 (S473); similar activation residues (S472 and S474, %respectively) are highly conserved in Akt2 and Akt3 Phosphoinositol-3-phosphate (PIP3) is a product of phosphoinositol 3-kinase enzymatic activity and has been shown to be a prerequisite lipid modulator of Akt activity Akt activity can be regulated by the PTEN tumour suppressor gene, which negatively regulates PIP3 levels PIP3 has been described as a downstream component of a wide range of receptors, including the c-Met receptor [5], the epidermal growth factor receptor family [6], fibroblast growth factor receptor [7], insulin growth factor receptor [8] and platelet-derived growth factor receptor PubMed:15987444

p(HGNC:AKT1, pmod(Ph, Ser, 473)) directlyIncreases act(p(HGNC:AKT1), ma(kin))

mTORC2 can be activated by PI3K directly and phosphorylates Akt at S473, which together with phosphorylation at T308 results in the full activation of Akt [12,13]. PubMed:17200144

p(HGNC:AKT1, pmod(Ph, Ser, 473)) directlyIncreases act(p(HGNC:AKT1), ma(kin))

Phosphorylation at Ser473 in the hydrophobic motif, along with Thr308 in its activation loop, is considered necessary for Akt function. PubMed:20691662

p(HGNC:AKT1, pmod(Ph, Ser, 473)) directlyIncreases act(p(HGNC:AKT1), ma(kin))

Furthermore, serum starvation-induced apoptosis caused a twofold increase in caspase 3 activity in C1-TEN-overexpressing cells vs. mock cells. In addition, C1-TEN-overexpressing cells showed a markedly reduced phosphorylation of Akt/PKB kinase and its substrate GSK3, as well as reduced Akt enzymatic activity. Equal amounts of total cell lysates were subjected to 10% SDSPAGE. The membrane was then probed with polyclonal antibody against GSK3 specifically phosphorylated at Ser21/9 (pGSK3?/?, CST), after which the membrane was stripped (stripping buffer, Pierce) and reprobed with polyclonal anti-total Akt antibody (CST). and Western blotting for detection of either Akt kinase specifically phosphorylated at Ser473 (pAkt) or both 42 and 44 kDa isoforms of phosphorylated ERK (pERK) using specific antibodies (Santa Cruz Biotechnology, Santa Cruz, CA). PubMed:15817639

p(HGNC:AKT1, pmod(Ph, Ser, 473)) directlyIncreases act(p(HGNC:AKT1), ma(kin))

Overexpressed IRS-3 as well as IRS-1 enhanced phosphoinositide (PI) 3-kinase activity in response to insulin and increased phosphorylation of protein kinase B (PKB) at S473 and phosphorylation of one of the members of the forkhead transcription factor FKHRL1 on T32 in both insulin-untreated and -treated states. PubMed:12504093

p(HGNC:AKT1, pmod(Ph, Ser, 473)) directlyIncreases act(p(HGNC:AKT1), ma(kin))

As shown in Fig. 2 B, subconfluent HeLa cultures have relatively low levels of active PKB, as detected by antibodies specifically recognizing PKB phosphorylated on serine 473. Phosphorylation of PKB is fully inhibitable by treatment with the specific PI 3-kinase inhibitor LY294002. Sparse cultures have barely detectable levels of phosphorylated PKB; however, dense cultures have much more activated PKB, whereas the total levels of PKB protein remain constant under all conditions examined. PubMed:11535620

p(HGNC:AKT1, pmod(Ph, Ser, 473)) directlyIncreases act(p(MGI:Akt1), ma(kin))

Thrombin induces the activation of platelet serine/threonine kinase Akt. Akt activation is dependent on its phosphorylation at threonine 308 and serine 473. PubMed:17883592

p(HGNC:AKT1, pmod(Ph, Ser, 473)) directlyIncreases act(p(MGI:Akt1), ma(kin))

Fig. 1. Insulin-like growth factor 1 (IGF-1)-mediated signaling pathways relevant to hypertrophy. Binding of IGF-1 activates the IGF-1 receptor (purple), which then recruits insulin-receptor substrate (IRS-1). This leads to the activation of two signaling pathways: the Ras-Raf-MEK-ERK pathway and the phosphatidylinositol 3-kinase (PI3K)- Akt pathway. The PI3K-Akt pathway recapitulates hypertrophy caused by IGF-1 stimulation. Akt1 activity can be modulated either by directly controlling its phosphorylation state or by altering the levels of the lipid that it binds at the cell membrane, phosphatidylinositol (3,4,5)-trisphosphate [PtdIns(3,4,5)P3] (orange). Signaling molecules that have been shown to have a negative effect on hypertrophy are colored red, and proteins whose activation induces hypertrophy are shown in green. Proteins that have not been assayed for their role in hypertrophy are shown in blue. Abbreviations: eIF-2B, eukaryotic translation initiation factor 2B; ERK, extracellular-signal-regulated kinase; GSK3b, glycogen-synthase kinase 3b; mTOR, mammalian target of rapamycin; p70S6K, p70 S6 kinase; PDK, phosphoinositide-dependent protein kinase; PtdIns(3,4)P2, phosphatidylinositol (3,4)-bisphosphate; PtdIns(4,5)P2, phosphatidylinositol (4,5)-bisphosphate; PHAS-1, phosphorylated heat- and acid-stable protein 1; PP2A, protein phosphatase 2A; PTEN, phosphatase and tensin homologous on chromosome 10; SHIP2, SH2-domain-containing inositol phosphatase; Tsc1/2, tuberous sclerosis complex 1 and 2. Modified from Ref. [87]. Akt1 activity can be modulated either by directly controlling its phosphorylation state or by altering the levels of the lipid that it binds at the cell membrane, PtdIns(3,4,5)P3 [22] (Fig. 1). Akt1 activity depends on phosphorylation at two sites: Ser473 and Thr309 [29]. PubMed:12928036

p(HGNC:AKT1, pmod(Ph, Ser, 473)) directlyIncreases act(p(MGI:Akt1), ma(kin))

Activation of PKB alpha and beta is then achieved at the plasma membrane by phosphorylation of Thr308/309 in the A-loop of the kinase domain and Ser473/474 in the carboxy-terminal regulatory region, respectively. The upstream kinase that phosphorylates PKB on Thr308, termed PI-dependent protein kinase-1, has been identified and extensively characterised. A candidate for the Ser473/474 kinase, termed the integrin-linked kinase, has been identified recently. PubMed:10454216

p(HGNC:AKT1, pmod(Ph, Ser, 473)) directlyIncreases act(p(MGI:Akt1), ma(kin))

Upon stimulation with insulin, AKT is recruited to cellular membranes by binding of its amino terminal pleckstrin (PH) domain to membrane bound phosphatidylinositol 3,4,5, trisphosphate (PIP3) [3]. The membrane bound form of AKT then becomes phosphorylated on two regulatory residues, a threonine within the activation loop (Thr308 in AKT1,Thr309 in AKT2, Thr305 in AKT3) and a serine in the C-terminus of the enzyme (Ser473 in AKT1,Ser474 in AKT2, Ser472 in AKT3), and both phosphorylations are considered to be required for AKT to reach maximum kinase activity [1]. The kinase responsible for phosphorylation of Thr308/309/305 has been identified as phosphoinositide-dependent kinase 1 (PDK1) [3]. PubMed:15890450

p(HGNC:AKT1, pmod(Ph, Ser, 473)) directlyIncreases act(p(MGI:Akt1), ma(kin))

The impact of IL-8 binding to AAT or HSA on its ability to stimulate Akt Ser473 phosphorylation, a key step in IL-8? mediated neutrophil chemotaxis (27), was explored. Figure 7D shows that IL-8 (1 ng) stimulated adequate Akt phosphorylation after just 10 minutes and that this effect was unaffected by prebinding of IL-8 to HSA (27.5 uM). PubMed:21060150

p(HGNC:AKT1, pmod(Ph, Ser, 473)) directlyIncreases act(p(MGI:Akt1), ma(kin))

In vivo 32P labeling and mutagenesis demonstrated that m/p-PKBalpha activity was due to phosphorylation on Thr308 and Ser473, that are normally induced on PKB following stimulation of the cells with insulin or insulin-like growth factor-1 (IGF-1).... Following activation the kinase detached from the membrane and translocated to the nucleus. PubMed:9395488

p(HGNC:AKT1, pmod(Ph, Ser, 473)) directlyIncreases act(p(MGI:Akt1), ma(kin))

Akt becomes activated upon phosphorylation of Ser473 and Thr308. In the absence of insulin, dexamethasone reduced Ser473 phosphorylation by 33% (P < 0.05 vs. no treatment, n = 3). PubMed:17229808

p(HGNC:AKT1, pmod(Ph, Ser, 473)) directlyIncreases act(p(MGI:Akt1), ma(kin))

three isoforms, AKT1 (PKBalpha), AKT2 (PKBbeta) and AKT3 (PKBgamma) they all contain a central kinase domain with an activation-loop phosphorylation site, Thr308, and a conserved, regulatory C-terminal phosphorylation site, Ser473 PubMed:12044776

p(HGNC:AKT1, pmod(Ph, Ser, 473)) directlyIncreases act(p(MGI:Akt1), ma(kin))

Furthermore, we show that inhibition of mTOR by rapamycin induces the activation of Akt as shown by increased Akt phosphorylation at Ser(473) and the inhibition of 6-TG-induced apoptosis and cell death. Activated Akt is a well-known inhibitor of autophagy. PubMed:18381446

p(HGNC:AKT1, pmod(Ph, Ser, 473)) directlyIncreases act(p(MGI:Akt1), ma(kin))

Stimulation of platelets with a PAR1-activating peptide (SFLLRN), PAR4-activating peptide (AYPGKF), and thrombin resulted in Thr308 and Ser473 phosphorylation of Akt, which results in its activation. PubMed:14623889

p(HGNC:AKT1, pmod(Ph, Ser, 473)) directlyIncreases act(p(MGI:Akt1), ma(kin))

After PIP3 binding, Akt1 is activated by phosphorylation on two critical residues, namely threonine %308 (T308) and serine 473 (S473); similar activation residues (S472 and S474, %respectively) are highly conserved in Akt2 and Akt3 Phosphoinositol-3-phosphate (PIP3) is a product of phosphoinositol 3-kinase enzymatic activity and has been shown to be a prerequisite lipid modulator of Akt activity Akt activity can be regulated by the PTEN tumour suppressor gene, which negatively regulates PIP3 levels PIP3 has been described as a downstream component of a wide range of receptors, including the c-Met receptor [5], the epidermal growth factor receptor family [6], fibroblast growth factor receptor [7], insulin growth factor receptor [8] and platelet-derived growth factor receptor PubMed:15987444

p(HGNC:AKT1, pmod(Ph, Ser, 473)) directlyIncreases act(p(MGI:Akt1), ma(kin))

mTORC2 can be activated by PI3K directly and phosphorylates Akt at S473, which together with phosphorylation at T308 results in the full activation of Akt [12,13]. PubMed:17200144

p(HGNC:AKT1, pmod(Ph, Ser, 473)) directlyIncreases act(p(MGI:Akt1), ma(kin))

Phosphorylation at Ser473 in the hydrophobic motif, along with Thr308 in its activation loop, is considered necessary for Akt function. PubMed:20691662

p(HGNC:AKT1, pmod(Ph, Ser, 473)) directlyIncreases act(p(MGI:Akt1), ma(kin))

Furthermore, serum starvation-induced apoptosis caused a twofold increase in caspase 3 activity in C1-TEN-overexpressing cells vs. mock cells. In addition, C1-TEN-overexpressing cells showed a markedly reduced phosphorylation of Akt/PKB kinase and its substrate GSK3, as well as reduced Akt enzymatic activity. Equal amounts of total cell lysates were subjected to 10% SDSPAGE. The membrane was then probed with polyclonal antibody against GSK3 specifically phosphorylated at Ser21/9 (pGSK3?/?, CST), after which the membrane was stripped (stripping buffer, Pierce) and reprobed with polyclonal anti-total Akt antibody (CST). and Western blotting for detection of either Akt kinase specifically phosphorylated at Ser473 (pAkt) or both 42 and 44 kDa isoforms of phosphorylated ERK (pERK) using specific antibodies (Santa Cruz Biotechnology, Santa Cruz, CA). PubMed:15817639

p(HGNC:AKT1, pmod(Ph, Ser, 473)) directlyIncreases act(p(MGI:Akt1), ma(kin))

Overexpressed IRS-3 as well as IRS-1 enhanced phosphoinositide (PI) 3-kinase activity in response to insulin and increased phosphorylation of protein kinase B (PKB) at S473 and phosphorylation of one of the members of the forkhead transcription factor FKHRL1 on T32 in both insulin-untreated and -treated states. PubMed:12504093

p(HGNC:AKT1, pmod(Ph, Ser, 473)) directlyIncreases act(p(MGI:Akt1), ma(kin))

As shown in Fig. 2 B, subconfluent HeLa cultures have relatively low levels of active PKB, as detected by antibodies specifically recognizing PKB phosphorylated on serine 473. Phosphorylation of PKB is fully inhibitable by treatment with the specific PI 3-kinase inhibitor LY294002. Sparse cultures have barely detectable levels of phosphorylated PKB; however, dense cultures have much more activated PKB, whereas the total levels of PKB protein remain constant under all conditions examined. PubMed:11535620

p(HGNC:AKT1, pmod(Ph, Ser, 473)) directlyIncreases act(p(RGD:Akt1), ma(kin))

Thrombin induces the activation of platelet serine/threonine kinase Akt. Akt activation is dependent on its phosphorylation at threonine 308 and serine 473. PubMed:17883592

p(HGNC:AKT1, pmod(Ph, Ser, 473)) directlyIncreases act(p(RGD:Akt1), ma(kin))

Fig. 1. Insulin-like growth factor 1 (IGF-1)-mediated signaling pathways relevant to hypertrophy. Binding of IGF-1 activates the IGF-1 receptor (purple), which then recruits insulin-receptor substrate (IRS-1). This leads to the activation of two signaling pathways: the Ras-Raf-MEK-ERK pathway and the phosphatidylinositol 3-kinase (PI3K)- Akt pathway. The PI3K-Akt pathway recapitulates hypertrophy caused by IGF-1 stimulation. Akt1 activity can be modulated either by directly controlling its phosphorylation state or by altering the levels of the lipid that it binds at the cell membrane, phosphatidylinositol (3,4,5)-trisphosphate [PtdIns(3,4,5)P3] (orange). Signaling molecules that have been shown to have a negative effect on hypertrophy are colored red, and proteins whose activation induces hypertrophy are shown in green. Proteins that have not been assayed for their role in hypertrophy are shown in blue. Abbreviations: eIF-2B, eukaryotic translation initiation factor 2B; ERK, extracellular-signal-regulated kinase; GSK3b, glycogen-synthase kinase 3b; mTOR, mammalian target of rapamycin; p70S6K, p70 S6 kinase; PDK, phosphoinositide-dependent protein kinase; PtdIns(3,4)P2, phosphatidylinositol (3,4)-bisphosphate; PtdIns(4,5)P2, phosphatidylinositol (4,5)-bisphosphate; PHAS-1, phosphorylated heat- and acid-stable protein 1; PP2A, protein phosphatase 2A; PTEN, phosphatase and tensin homologous on chromosome 10; SHIP2, SH2-domain-containing inositol phosphatase; Tsc1/2, tuberous sclerosis complex 1 and 2. Modified from Ref. [87]. Akt1 activity can be modulated either by directly controlling its phosphorylation state or by altering the levels of the lipid that it binds at the cell membrane, PtdIns(3,4,5)P3 [22] (Fig. 1). Akt1 activity depends on phosphorylation at two sites: Ser473 and Thr309 [29]. PubMed:12928036

p(HGNC:AKT1, pmod(Ph, Ser, 473)) directlyIncreases act(p(RGD:Akt1), ma(kin))

Activation of PKB alpha and beta is then achieved at the plasma membrane by phosphorylation of Thr308/309 in the A-loop of the kinase domain and Ser473/474 in the carboxy-terminal regulatory region, respectively. The upstream kinase that phosphorylates PKB on Thr308, termed PI-dependent protein kinase-1, has been identified and extensively characterised. A candidate for the Ser473/474 kinase, termed the integrin-linked kinase, has been identified recently. PubMed:10454216

p(HGNC:AKT1, pmod(Ph, Ser, 473)) directlyIncreases act(p(RGD:Akt1), ma(kin))

Upon stimulation with insulin, AKT is recruited to cellular membranes by binding of its amino terminal pleckstrin (PH) domain to membrane bound phosphatidylinositol 3,4,5, trisphosphate (PIP3) [3]. The membrane bound form of AKT then becomes phosphorylated on two regulatory residues, a threonine within the activation loop (Thr308 in AKT1,Thr309 in AKT2, Thr305 in AKT3) and a serine in the C-terminus of the enzyme (Ser473 in AKT1,Ser474 in AKT2, Ser472 in AKT3), and both phosphorylations are considered to be required for AKT to reach maximum kinase activity [1]. The kinase responsible for phosphorylation of Thr308/309/305 has been identified as phosphoinositide-dependent kinase 1 (PDK1) [3]. PubMed:15890450

p(HGNC:AKT1, pmod(Ph, Ser, 473)) directlyIncreases act(p(RGD:Akt1), ma(kin))

The impact of IL-8 binding to AAT or HSA on its ability to stimulate Akt Ser473 phosphorylation, a key step in IL-8? mediated neutrophil chemotaxis (27), was explored. Figure 7D shows that IL-8 (1 ng) stimulated adequate Akt phosphorylation after just 10 minutes and that this effect was unaffected by prebinding of IL-8 to HSA (27.5 uM). PubMed:21060150

p(HGNC:AKT1, pmod(Ph, Ser, 473)) directlyIncreases act(p(RGD:Akt1), ma(kin))

In vivo 32P labeling and mutagenesis demonstrated that m/p-PKBalpha activity was due to phosphorylation on Thr308 and Ser473, that are normally induced on PKB following stimulation of the cells with insulin or insulin-like growth factor-1 (IGF-1).... Following activation the kinase detached from the membrane and translocated to the nucleus. PubMed:9395488

p(HGNC:AKT1, pmod(Ph, Ser, 473)) directlyIncreases act(p(RGD:Akt1), ma(kin))

Akt becomes activated upon phosphorylation of Ser473 and Thr308. In the absence of insulin, dexamethasone reduced Ser473 phosphorylation by 33% (P < 0.05 vs. no treatment, n = 3). PubMed:17229808

p(HGNC:AKT1, pmod(Ph, Ser, 473)) directlyIncreases act(p(RGD:Akt1), ma(kin))

three isoforms, AKT1 (PKBalpha), AKT2 (PKBbeta) and AKT3 (PKBgamma) they all contain a central kinase domain with an activation-loop phosphorylation site, Thr308, and a conserved, regulatory C-terminal phosphorylation site, Ser473 PubMed:12044776

p(HGNC:AKT1, pmod(Ph, Ser, 473)) directlyIncreases act(p(RGD:Akt1), ma(kin))

Furthermore, we show that inhibition of mTOR by rapamycin induces the activation of Akt as shown by increased Akt phosphorylation at Ser(473) and the inhibition of 6-TG-induced apoptosis and cell death. Activated Akt is a well-known inhibitor of autophagy. PubMed:18381446

p(HGNC:AKT1, pmod(Ph, Ser, 473)) directlyIncreases act(p(RGD:Akt1), ma(kin))

Stimulation of platelets with a PAR1-activating peptide (SFLLRN), PAR4-activating peptide (AYPGKF), and thrombin resulted in Thr308 and Ser473 phosphorylation of Akt, which results in its activation. PubMed:14623889

p(HGNC:AKT1, pmod(Ph, Ser, 473)) directlyIncreases act(p(RGD:Akt1), ma(kin))

After PIP3 binding, Akt1 is activated by phosphorylation on two critical residues, namely threonine %308 (T308) and serine 473 (S473); similar activation residues (S472 and S474, %respectively) are highly conserved in Akt2 and Akt3 Phosphoinositol-3-phosphate (PIP3) is a product of phosphoinositol 3-kinase enzymatic activity and has been shown to be a prerequisite lipid modulator of Akt activity Akt activity can be regulated by the PTEN tumour suppressor gene, which negatively regulates PIP3 levels PIP3 has been described as a downstream component of a wide range of receptors, including the c-Met receptor [5], the epidermal growth factor receptor family [6], fibroblast growth factor receptor [7], insulin growth factor receptor [8] and platelet-derived growth factor receptor PubMed:15987444

p(HGNC:AKT1, pmod(Ph, Ser, 473)) directlyIncreases act(p(RGD:Akt1), ma(kin))

mTORC2 can be activated by PI3K directly and phosphorylates Akt at S473, which together with phosphorylation at T308 results in the full activation of Akt [12,13]. PubMed:17200144

p(HGNC:AKT1, pmod(Ph, Ser, 473)) directlyIncreases act(p(RGD:Akt1), ma(kin))

Phosphorylation at Ser473 in the hydrophobic motif, along with Thr308 in its activation loop, is considered necessary for Akt function. PubMed:20691662

p(HGNC:AKT1, pmod(Ph, Ser, 473)) directlyIncreases act(p(RGD:Akt1), ma(kin))

Furthermore, serum starvation-induced apoptosis caused a twofold increase in caspase 3 activity in C1-TEN-overexpressing cells vs. mock cells. In addition, C1-TEN-overexpressing cells showed a markedly reduced phosphorylation of Akt/PKB kinase and its substrate GSK3, as well as reduced Akt enzymatic activity. Equal amounts of total cell lysates were subjected to 10% SDSPAGE. The membrane was then probed with polyclonal antibody against GSK3 specifically phosphorylated at Ser21/9 (pGSK3?/?, CST), after which the membrane was stripped (stripping buffer, Pierce) and reprobed with polyclonal anti-total Akt antibody (CST). and Western blotting for detection of either Akt kinase specifically phosphorylated at Ser473 (pAkt) or both 42 and 44 kDa isoforms of phosphorylated ERK (pERK) using specific antibodies (Santa Cruz Biotechnology, Santa Cruz, CA). PubMed:15817639

p(HGNC:AKT1, pmod(Ph, Ser, 473)) directlyIncreases act(p(RGD:Akt1), ma(kin))

Overexpressed IRS-3 as well as IRS-1 enhanced phosphoinositide (PI) 3-kinase activity in response to insulin and increased phosphorylation of protein kinase B (PKB) at S473 and phosphorylation of one of the members of the forkhead transcription factor FKHRL1 on T32 in both insulin-untreated and -treated states. PubMed:12504093

p(HGNC:AKT1, pmod(Ph, Ser, 473)) directlyIncreases act(p(RGD:Akt1), ma(kin))

As shown in Fig. 2 B, subconfluent HeLa cultures have relatively low levels of active PKB, as detected by antibodies specifically recognizing PKB phosphorylated on serine 473. Phosphorylation of PKB is fully inhibitable by treatment with the specific PI 3-kinase inhibitor LY294002. Sparse cultures have barely detectable levels of phosphorylated PKB; however, dense cultures have much more activated PKB, whereas the total levels of PKB protein remain constant under all conditions examined. PubMed:11535620

p(HGNC:AKT1, pmod(Ph, Ser, 473)) biomarkerFor bp(MESHPP:"Insulin Resistance")

Abnormal phosphorylation of tau and activation of μ-calpain are two key events in the pathology of AD. Importantly, these two events are also related with GCs and IR Importantly, these two events are also related with GCs and IR. We therefore speculate that tau phosphorylation and μ-calpain activation may mediate the GCs-induced IR. Akt phosphorylation at Ser-473 (pAkt) is commonly used as a marker for assessing IR. PubMed:22536436

Annotations
Disease Ontology (DO)
Alzheimer's disease
NeuroMMSigDB
Akt subgraph
NeuroMMSigDB
Insulin signal transduction

p(HGNC:AKT1, pmod(Ph, Ser, 473)) decreases bp(GOBP:autophagy)

Furthermore, we show that inhibition of mTOR by rapamycin induces the activation of Akt as shown by increased Akt phosphorylation at Ser(473) and the inhibition of 6-TG-induced apoptosis and cell death. Activated Akt is a well-known inhibitor of autophagy. PubMed:18381446

p(HGNC:AKT1, pmod(Ph, Ser, 473)) directlyIncreases act(p(HGNC:AKT1), ma(kin))

Furthermore, we show that inhibition of mTOR by rapamycin induces the activation of Akt as shown by increased Akt phosphorylation at Ser(473) and the inhibition of 6-TG-induced apoptosis and cell death. Activated Akt is a well-known inhibitor of autophagy. PubMed:18381446

p(HGNC:AKT1, pmod(Ph, Ser, 473)) biomarkerFor bp(MESHPP:"Insulin Resistance")

Abnormal phosphorylation of tau and activation of mu-calpain are two key events in the pathology of AD. Importantly, these two events are also related with GCs and IR. We therefore speculate that tau phosphorylation and mu-calpain activation may mediate the GCs-induced IR. Akt phosphorylation at Ser-473 (pAkt) is commonly used as a marker for assessing IR. PubMed:22536436

act(p(HGNC:AKT1, pmod(Ph, Ser, 473)), ma(kin)) association path(MESHD:"Colorectal Neoplasms")

A constitutive activation of protein kinase B (AKT) in a hyper-phosphorylated status at Ser473 is one of the hallmarks of anti-EGFR therapy-resistant colorectal cancer (CRC). PubMed:25365190

Annotations
NCBI Taxonomy Ids
9606
Experimental Factor Ontology (EFO)
COLO 205 cell
Experimental Factor Ontology (EFO)
HT-29
Disease Ontology (DO)
colorectal cancer
MeSH
Rectal Neoplasms

act(p(HGNC:AKT1, pmod(Ph, Ser, 473)), ma(kin)) association path(MESHD:"Colorectal Neoplasms")

A constitutive activation of protein kinase B (AKT) in a hyper-phosphorylated status at Ser473 is one of the hallmarks of anti-EGFR therapy-resistant colorectal cancer (CRC). PubMed:25365190

Annotations
MeSH
Microtubules
Experimental Factor Ontology (EFO)
COLO 205 cell
Experimental Factor Ontology (EFO)
HT-29
MeSH
Rectal Neoplasms
Evidence and Conclusion Ontology
immunohistochemistry
MeSH
Plasma
NCBI Taxonomy Names
Mus musculus
Disease Ontology (DO)
colorectal cancer
NCBI Taxonomy Ids
9606

p(HGNC:AKT1, pmod(Ph, Ser, 473)) decreases bp(GOBP:autophagy)

Furthermore, we show that inhibition of mTOR by rapamycin induces the activation of Akt as shown by increased Akt phosphorylation at Ser(473) and the inhibition of 6-TG-induced apoptosis and cell death. Activated Akt is a well-known inhibitor of autophagy. PubMed:18381446

p(HGNC:AKT1, pmod(Ph, Ser, 473)) directlyIncreases act(p(HGNC:AKT1), ma(kin))

Furthermore, we show that inhibition of mTOR by rapamycin induces the activation of Akt as shown by increased Akt phosphorylation at Ser(473) and the inhibition of 6-TG-induced apoptosis and cell death. Activated Akt is a well-known inhibitor of autophagy. PubMed:18381446

act(p(HGNC:AKT1, pmod(Ph, Ser, 473)), ma(kin)) association path(MESHD:"Colorectal Neoplasms")

A constitutive activation of protein kinase B (AKT) in a hyper-phosphorylated status at Ser473 is one of the hallmarks of anti-EGFR therapy-resistant colorectal cancer (CRC). PubMed:25365190

p(HGNC:AKT1, pmod(Ph, Ser, 473)) decreases bp(GOBP:autophagy)

Furthermore, we show that inhibition of mTOR by rapamycin induces the activation of Akt as shown by increased Akt phosphorylation at Ser(473) and the inhibition of 6-TG-induced apoptosis and cell death. Activated Akt is a well-known inhibitor of autophagy. PubMed:18381446

Appears in Networks:
Annotations
MeSH
Cytoplasm
MeSH
Condylomata Acuminata
Evidence and Conclusion Ontology
immunohistochemistry
MeSH
Plasma
NCBI Taxonomy Names
Mus musculus
NCBI Taxonomy Ids
9606

p(HGNC:AKT1, pmod(Ph, Ser, 473)) directlyIncreases act(p(HGNC:AKT1), ma(kin))

Furthermore, we show that inhibition of mTOR by rapamycin induces the activation of Akt as shown by increased Akt phosphorylation at Ser(473) and the inhibition of 6-TG-induced apoptosis and cell death. Activated Akt is a well-known inhibitor of autophagy. PubMed:18381446

Appears in Networks:
Annotations
MeSH
Cytoplasm
MeSH
Condylomata Acuminata
Evidence and Conclusion Ontology
immunohistochemistry
MeSH
Plasma
NCBI Taxonomy Names
Mus musculus
NCBI Taxonomy Ids
9606

p(HGNC:AKT1, pmod(Ph, Ser, 473)) directlyIncreases act(p(HGNC:AKT1), ma(kin))

Furthermore, we show that inhibition of mTOR by rapamycin induces the activation of Akt as shown by increased Akt phosphorylation at Ser(473) and the inhibition of 6-TG-induced apoptosis and cell death. Activated Akt is a well-known inhibitor of autophagy. PubMed:18381446

Annotations
Experimental Factor Ontology (EFO)
NCI-H1299 cell
MeSH
Cytoplasm
MeSH
Lung Neoplasms
MeSH
Lung
Cell Ontology (CL)
stem cell
NCBI Taxonomy Ids
9606

act(p(HGNC:AKT1, pmod(Ph, Ser, 473)), ma(kin)) association p(HGNC:PIK3CA, var(p.Pro499Thr))

The aim of this study was to examine the role of cytosolic phospholipase A2α (cPLA2α) on AKT phosphorylation at Ser473 and cell proliferation in CRC cells with mutation in phosphoinositide 3-kinase (PI3K). AKT phosphorylation at Ser473 was resistant to EGF stimulation in CRC cell lines of DLD-1 (PIK3CAE545K mutation) and HT-29 (PIK3CAP499T mutation). Over-expression of cPLA2α by stable transfection increased basal and EGF-stimulated AKT phosphorylation and proliferation in DLD-1 cells. PubMed:25365190

Annotations
Experimental Factor Ontology (EFO)
COLO 205 cell
Experimental Factor Ontology (EFO)
HT-29
MeSH
Intracellular Space
MeSH
Rectal Neoplasms
MeSH
Mucus
NCBI Taxonomy Names
Crataegus azarolus
Disease Ontology (DO)
colorectal cancer
Uberon
intestinal epithelium
Cell Ontology (CL)
stem cell
NCBI Taxonomy Ids
9606

act(p(HGNC:AKT1, pmod(Ph, Ser, 473)), ma(kin)) association path(MESHD:"Colorectal Neoplasms")

A constitutive activation of protein kinase B (AKT) in a hyper-phosphorylated status at Ser473 is one of the hallmarks of anti-EGFR therapy-resistant colorectal cancer (CRC). PubMed:25365190

Annotations
Experimental Factor Ontology (EFO)
COLO 205 cell
Experimental Factor Ontology (EFO)
HT-29
MeSH
Intracellular Space
MeSH
Rectal Neoplasms
MeSH
Mucus
NCBI Taxonomy Names
Crataegus azarolus
Disease Ontology (DO)
colorectal cancer
Uberon
intestinal epithelium
Cell Ontology (CL)
stem cell
NCBI Taxonomy Ids
9606

p(HGNC:AKT1, pmod(Ph, Ser, 473)) decreases bp(GOBP:autophagy)

Furthermore, we show that inhibition of mTOR by rapamycin induces the activation of Akt as shown by increased Akt phosphorylation at Ser(473) and the inhibition of 6-TG-induced apoptosis and cell death. Activated Akt is a well-known inhibitor of autophagy. PubMed:18381446

Annotations
Experimental Factor Ontology (EFO)
NCI-H1299 cell
MeSH
Cytoplasm
MeSH
Lung Neoplasms
MeSH
Lung
Cell Ontology (CL)
stem cell
NCBI Taxonomy Ids
9606

act(p(HGNC:AKT1, pmod(Ph, Ser, 473)), ma(kin)) association bp(MESHPP:"Drug Resistance")

A constitutive activation of protein kinase B (AKT) in a hyper-phosphorylated status at Ser473 is one of the hallmarks of anti-EGFR therapy-resistant colorectal cancer (CRC). PubMed:25365190

Annotations
Experimental Factor Ontology (EFO)
COLO 205 cell
Experimental Factor Ontology (EFO)
HT-29
MeSH
Intracellular Space
MeSH
Rectal Neoplasms
MeSH
Mucus
NCBI Taxonomy Names
Crataegus azarolus
Disease Ontology (DO)
colorectal cancer
Uberon
intestinal epithelium
Cell Ontology (CL)
stem cell
NCBI Taxonomy Ids
9606

act(p(HGNC:AKT1, pmod(Ph, Ser, 473)), ma(kin)) association p(HGNC:PIK3CA, var(p.Glu545Lys))

The aim of this study was to examine the role of cytosolic phospholipase A2α (cPLA2α) on AKT phosphorylation at Ser473 and cell proliferation in CRC cells with mutation in phosphoinositide 3-kinase (PI3K). AKT phosphorylation at Ser473 was resistant to EGF stimulation in CRC cell lines of DLD-1 (PIK3CAE545K mutation) and HT-29 (PIK3CAP499T mutation). Over-expression of cPLA2α by stable transfection increased basal and EGF-stimulated AKT phosphorylation and proliferation in DLD-1 cells. PubMed:25365190

Annotations
Experimental Factor Ontology (EFO)
COLO 205 cell
Experimental Factor Ontology (EFO)
HT-29
MeSH
Intracellular Space
MeSH
Rectal Neoplasms
MeSH
Mucus
NCBI Taxonomy Names
Crataegus azarolus
Disease Ontology (DO)
colorectal cancer
Uberon
intestinal epithelium
Cell Ontology (CL)
stem cell
NCBI Taxonomy Ids
9606

p(HGNC:AKT1, pmod(Ph, Ser, 473)) directlyIncreases act(p(HGNC:AKT1), ma(kin))

Furthermore, we show that inhibition of mTOR by rapamycin induces the activation of Akt as shown by increased Akt phosphorylation at Ser(473) and the inhibition of 6-TG-induced apoptosis and cell death. Activated Akt is a well-known inhibitor of autophagy. PubMed:18381446

act(p(HGNC:AKT1, pmod(Ph, Ser, 473)), ma(kin)) association p(HGNC:PIK3CA, var(p.Pro499Thr))

The aim of this study was to examine the role of cytosolic phospholipase A2α (cPLA2α) on AKT phosphorylation at Ser473 and cell proliferation in CRC cells with mutation in phosphoinositide 3-kinase (PI3K). AKT phosphorylation at Ser473 was resistant to EGF stimulation in CRC cell lines of DLD-1 (PIK3CAE545K mutation) and HT-29 (PIK3CAP499T mutation). Over-expression of cPLA2α by stable transfection increased basal and EGF-stimulated AKT phosphorylation and proliferation in DLD-1 cells. PubMed:25365190

p(HGNC:AKT1, pmod(Ph, Ser, 473)) decreases bp(GOBP:autophagy)

Furthermore, we show that inhibition of mTOR by rapamycin induces the activation of Akt as shown by increased Akt phosphorylation at Ser(473) and the inhibition of 6-TG-induced apoptosis and cell death. Activated Akt is a well-known inhibitor of autophagy. PubMed:18381446

act(p(HGNC:AKT1, pmod(Ph, Ser, 473)), ma(kin)) association bp(MESHPP:"Drug Resistance")

A constitutive activation of protein kinase B (AKT) in a hyper-phosphorylated status at Ser473 is one of the hallmarks of anti-EGFR therapy-resistant colorectal cancer (CRC). PubMed:25365190

act(p(HGNC:AKT1, pmod(Ph, Ser, 473)), ma(kin)) association p(HGNC:PIK3CA, var(p.Glu545Lys))

The aim of this study was to examine the role of cytosolic phospholipase A2α (cPLA2α) on AKT phosphorylation at Ser473 and cell proliferation in CRC cells with mutation in phosphoinositide 3-kinase (PI3K). AKT phosphorylation at Ser473 was resistant to EGF stimulation in CRC cell lines of DLD-1 (PIK3CAE545K mutation) and HT-29 (PIK3CAP499T mutation). Over-expression of cPLA2α by stable transfection increased basal and EGF-stimulated AKT phosphorylation and proliferation in DLD-1 cells. PubMed:25365190

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