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Entity

Name
PLAU
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 16

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

Growth Factor-2.0-Hs v2.0

The Growth Factor network depicts the causal mechanisms of common extracellular growth factors involved in regulating lung cell proliferation, namely EGF, TGF-beta, VEGF, and FGF family members. The EGF family members EGF and TGF-alpha play critical roles in regulating the proliferation of airway epithelial cells through EGF receptor activation. FGF7 and FGF10, largely through activation of FGFR2 signaling, stimulate lung epithelial cell proliferation as well as regulate branching morphogenesis in the developing lung. VEGF, a key regulator of normal angiogenesis that is also involved in regulating proliferation of human fetal airway epithelial cells, was also included in the network. \nReviewed during Jamboree2014

Hox-2.0-Hs v2.0

The Hox network describes the causal mechanisms in the Hox signaling pathway that leads to cell proliferation as well as downstream targets of the HOX family members such as CDKN1A, CDKN1B, CDKN1C, ITGAV, and ITGB3.

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.

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 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

In-Edges 53

act(p(HGNC:RSL1D1), ma(cat)) increases p(HGNC:PLAU)

Western blotting and Enzyme-linked immunoadsordent assay further confirmed that PBK1 can upregulate the expression of uPA. PubMed:15880258

Annotations
Experimental Factor Ontology (EFO)
C6 cell
NCBI Taxonomy Ids
9606
Uberon
kidney
Cell Ontology (CL)
dendritic cell
MeSH
Cell Membrane
Disease Ontology (DO)
hypertension
MeSH
Sputum
MeSH
Head and Neck Neoplasms

act(p(HGNC:HRAS), ma(gtp)) decreases act(p(HGNC:PLAU), ma(cat))

However, expression and activity of the metastatic gene uPA and invasive capacity of the cells were significantly reduced by the oncogene RAS. PubMed:15618232

Annotations
Experimental Factor Ontology (EFO)
U-87 MG cell
NCBI Taxonomy Ids
9606
Uberon
breast
Cell Ontology (CL)
fibroblast
MeSH
Cytoplasm
Disease Ontology (DO)
prostate cancer
MeSH
Sputum
MeSH
Head and Neck Neoplasms

tloc(p(HGNC:PLAU), fromLoc(GOCCID:0005886), toLoc(GOCCID:0005737)) increases act(p(HGNC:PLAU), ma(cat))

PAs mitogenic stimulation of serum-starved cells was associated with the internalization of their molecules PubMed:10801075

Annotations
Experimental Factor Ontology (EFO)
U-937 cell
NCBI Taxonomy Ids
9606
Uberon
adipose tissue
Cell Ontology (CL)
neuron
MeSH
Cell Membrane
Disease Ontology (DO)
breast cancer

act(p(HGNC:MMP3), ma(cat)) increases p(HGNC:PLAU)

Several molecular interactions between the matrix metalloproteinase (MMP) and the plasminogen/plasmin (fibrinolytic) system may affect cellular fibrinolysis. MMP-3 (stromelysin-1) specifically hydrolyzes urokinase (u-PA), yielding a 17 kD NH2-terminal fragment containing the functionally intact receptor (u-PAR)-binding sequence and a 32 kD COOH-terminal fragment containing the intact serine proteinase domain. PubMed:11841344

Annotations
Experimental Factor Ontology (EFO)
LNCAP cell
NCBI Taxonomy Ids
9606
Uberon
prostate gland
Cell Ontology (CL)
T cell
MeSH
Extracellular Space
Disease Ontology (DO)
endometrial cancer

p(HGNC:EGF) increases tloc(p(HGNC:PLAU), fromLoc(GOCC:intracellular), toLoc(GOCC:"extracellular space"))

(4) the EGF-induced cell migration was statistically higher inAR negative than in AR positive cells with a similar increase with respect to basal value (about 2.6 fold); (5) the Matrigel invasion was statistically higher in AR negative than in AR positive PCa cells also if the increment of Matrigel invasion after EGF treatment was statistically higher in AR positive respect to AR negative cells; (6) the EGF induced uPA secretion and its membrane uptake through the increment of uPAR; PubMed:15886816

Annotations
Experimental Factor Ontology (EFO)
HL-60 cell
NCBI Taxonomy Ids
9606
Uberon
large intestine
Cell Ontology (CL)
muscle cell
MeSH
Cell Membrane
Disease Ontology (DO)
multiple myeloma
MeSH
Sputum
MeSH
Head and Neck Neoplasms

p(HGNC:FGF2) increases act(p(HGNC:PLAU), ma(cat))

Also, FGFs modulate the expression of uPA receptor on the endothelial cell surface, thus allowing the localization of the proteolytic activity at the leading edge of the cell at the front of migration [22]. Furthermore, FGF1 and FGF2 induce the expression of the plasminogen activator inhibitor (PAI)-1 in cultured endothelial cells leading to a fine modulation of the proteolytic balance [23-25]. PubMed:15863032

Annotations
Experimental Factor Ontology (EFO)
PC-12 cell
NCBI Taxonomy Ids
9606
Uberon
skeletal muscle tissue
Cell Ontology (CL)
megakaryocyte
MeSH
Cell Membrane
Disease Ontology (DO)
neuroblastoma
MeSH
Sputum
MeSH
Head and Neck Neoplasms

p(HGNC:FGF2) increases act(p(HGNC:PLAU), ma(cat))

PKC downregulation abolishes FGF2-induced endothelial cell proliferation but not urokinase-type plasminogen activator (uPA) upregulation. PubMed:15863032

Annotations
Experimental Factor Ontology (EFO)
PC-12 cell
NCBI Taxonomy Ids
9606
Uberon
cardiovascular system endothelium
Cell Ontology (CL)
megakaryocyte
MeSH
Cell Membrane
Disease Ontology (DO)
neuroblastoma
MeSH
Sputum
MeSH
Head and Neck Neoplasms

act(p(HGNC:PLAUR), ma(cat)) increases act(p(HGNC:PLAU), ma(cat))

Upon the binding of prourokinase to uPAR, prourokinase is converted to urokinase, which plays a critical role in initiating cell migration by degrading the extracellular components [14], a process that is essential for cell penetration through the extracellular matrix (ECM) during angiogenesis and tumor metastasis [15,16]. PubMed:15733059

Annotations
Experimental Factor Ontology (EFO)
HeLa cell
NCBI Taxonomy Ids
9606
Uberon
kidney
Cell Ontology (CL)
T cell
MeSH
Cell Nucleus
Disease Ontology (DO)
liver cancer
MeSH
Sputum
MeSH
Head and Neck Neoplasms

p(HGNC:SPP1) increases tloc(p(HGNC:PLAU), fromLoc(GOCC:intracellular), toLoc(GOCC:"extracellular space"))

OPN also enhances uPA secretion, PubMed:12771144

Annotations
Experimental Factor Ontology (EFO)
U-937 cell
NCBI Taxonomy Ids
9606
Uberon
kidney
Cell Ontology (CL)
endothelial cell
MeSH
Cell Nucleus
Disease Ontology (DO)
lung cancer

p(HGNC:SERPINF2) directlyDecreases act(p(HGNC:PLAU), ma(cat))

PA activity is controlled at three levels: (i) the expression of uPA and uPAR is upregulated by angiogenic growth factors (88, 147) and cytokines (245). (ii) Pro-uPA needs to be activated proteolytically and (iii) the activity of plasmin and uPA is regulated by a 2-antiplasmin and plasminogen activator inhibitors (PAIs), respectively (11, 19). PubMed:11172729

Annotations
Experimental Factor Ontology (EFO)
293T/17 cell
NCBI Taxonomy Ids
9606
Uberon
endothelium
Cell Ontology (CL)
neutrophil
MeSH
Cell Nucleus
Disease Ontology (DO)
breast cancer

p(HGNC:IGF1) increases p(HGNC:PLAU)

Modified assertion PubMed:8827475

Annotations
Experimental Factor Ontology (EFO)
LNCAP cell
NCBI Taxonomy Ids
9606
Uberon
muscle tissue
Cell Ontology (CL)
osteoblast
MeSH
Cell Nucleus
Disease Ontology (DO)
cervical cancer
MeSH
Sputum
MeSH
Head and Neck Neoplasms

act(p(HGNC:MSR1), ma(cat)) increases act(p(HGNC:PLAU), ma(cat))

we demonstrate that binding of both lipoprotein and non-lipoprotein ligands to MSR-A induced protein tyrosine phosphorylation and increased protein kinase C (PKC) activity leading to up-regulated urokinase-type plasminogen activator (uPA) expression PubMed:9422792

Annotations
Experimental Factor Ontology (EFO)
COS-1 cell
NCBI Taxonomy Ids
9606
Uberon
prostate gland
Cell Ontology (CL)
muscle cell
MeSH
Cell Membrane
Disease Ontology (DO)
multiple myeloma
MeSH
Sputum
MeSH
Head and Neck Neoplasms

act(complex(p(HGNC:ITGAV), p(HGNC:ITGB3)), ma(cat)) increases p(HGNC:PLAU)

Similar to classical adhesive proteins, FGF2 binds avb3 [136]. Consequently, immobilized FGF2 promotes endothelial cell adhesion and spreading, leading to uPA upregulation, cell migration, proliferation, and morphogenesis [137]. PubMed:15863032

Annotations
Experimental Factor Ontology (EFO)
PC-12 cell
NCBI Taxonomy Ids
9606
Uberon
cardiovascular system endothelium
Cell Ontology (CL)
endothelial cell
MeSH
Cell Membrane
Disease Ontology (DO)
neuroblastoma
MeSH
Sputum
MeSH
Head and Neck Neoplasms

p(HGNC:HGF) increases p(HGNC:PLAU)

HGF induces the expression of uPA. When the HGF antibody or the tyrosine kinase inhibitor was introduced the uPA expression was decreased. PubMed:11408346

Annotations
Experimental Factor Ontology (EFO)
PC-12 cell
NCBI Taxonomy Ids
9606
Uberon
lung
Cell Ontology (CL)
fibroblast
MeSH
Cell Nucleus
Disease Ontology (DO)
fibrosarcoma

p(HGNC:HGF) increases p(HGNC:PLAU)

Modified assertion PubMed:9472107

Annotations
Experimental Factor Ontology (EFO)
HMEC
NCBI Taxonomy Ids
9606
Uberon
heart
Cell Ontology (CL)
platelet
MeSH
Extracellular Matrix
Disease Ontology (DO)
atherosclerosis
MeSH
Sputum
MeSH
Head and Neck Neoplasms

p(HGNC:NRG1) increases tloc(p(HGNC:PLAU), fromLoc(GOCC:intracellular), toLoc(GOCC:"extracellular space"))

HRG (heregulin) treatment of breast cancer cells was shown to increase expression of matrix metalloproteinase (MMP)-9 [128], as well as of the serine protease uPA and its receptor [129], leading to increased invasion. PubMed:12648469

Annotations
Experimental Factor Ontology (EFO)
HL-60 cell
NCBI Taxonomy Ids
9606
Uberon
blood plasma
Cell Ontology (CL)
fat cell
MeSH
Cytoplasm
Disease Ontology (DO)
multiple myeloma

act(complex(SCOMP:"Nfkb Complex"), ma(tscript)) increases act(p(HGNC:PLAU), ma(cat))

Modified assertion PubMed:12771144

Annotations
Experimental Factor Ontology (EFO)
U-937 cell
NCBI Taxonomy Ids
9606
Uberon
kidney
Cell Ontology (CL)
endothelial cell
MeSH
Cell Nucleus
Disease Ontology (DO)
lung cancer

p(HGNC:MAPK1) increases p(HGNC:PLAU)

u-PA-CAT expressed in combination with dominant negative mutant ERK construct abrogated the Urokinase-type plasminogen activator (uPA) promoter activity in PC3(AR) (AR transfected) cells. ERK dominant negative construct reduced the uPA promoter expression greater than 24-fold. Further, expression of dominant negative vectors PC4raf, CL100, and K97M for the ERK pathway reduced uPA protein expression by 75%, 82% and 57% respectively. This indicates that in MAPK pathway ERK represent a significant component in the regulation of uPA. PubMed:11676474

Annotations
Experimental Factor Ontology (EFO)
293 cell
NCBI Taxonomy Ids
9606
Uberon
heart
Cell Ontology (CL)
macrophage
MeSH
Cytoplasm
Disease Ontology (DO)
breast cancer

act(p(HGNC:PLG), ma(cat)) increases act(p(HGNC:PLAU), ma(cat))

uPA is secreted as an inactive single-chain proenzyme. Secreted pro-uPA binds to the uPA receptor (uPAR) present on many different cell types. Cleavage of pro-uPA by plasmin, Factor XIIa or cathepsin B yields the active enzyme consisting of two disulfide-linked chains (17). PubMed:11172729

Annotations
Experimental Factor Ontology (EFO)
293T/17 cell
NCBI Taxonomy Ids
9606
Uberon
endothelium
Cell Ontology (CL)
neutrophil
MeSH
Cell Nucleus
Disease Ontology (DO)
breast cancer

p(HGNC:PLG) increases act(p(HGNC:PLAU), ma(cat))

The single-chain urokinase (scuPA) secreted by cells has a low enzymatic activity which increases ~300-fold after the proteolytic cleavage of the Lys158-Ile159 bond [32] that results in uPA conversion into the two-chain form consisting of two polypeptide chains joined via the Cys148-Cys279 disulfide bond. The N-terminal A-chain includes the GFD and kringle domain; the B-chain contains the proteolytic domain. Plasmin is the most efficient activator of scuPA, although the other enzymes (kallikrein, trypsin, blood coagulation factor XIIa, and cathepsin in tumor cells [32]) could potentially compensate for any loss of plasmin function. In addition to spatial control of extracellular proteolysis, the urokinase receptor is involved in the activation and inactivation of urokinase. The binding of the secreted single-chain urokinase to the uPAR makes it more sensitive to proteolytic activation by plasmin than the free urokinase [35]. PubMed:11841347

Annotations
Experimental Factor Ontology (EFO)
Saos-2 cell
NCBI Taxonomy Ids
9606
Uberon
smooth muscle tissue
Cell Ontology (CL)
smooth muscle cell
MeSH
Extracellular Space
Disease Ontology (DO)
atherosclerosis

act(p(HGNC:PLG), ma(cat)) increases act(p(HGNC:PLAU), ma(cat))

Several types of proteolytic enzymes have been identified to specifically degrade the proteins of the extracellular matrix: matrix metalloproteinases (MMPs) [5], cysteine proteases [6], and serine proteases [7]. Serine protease urokinase-type plasminogen activator (uPA) is a protease that cleaves the extracellular matrix and stimulates the conversion of plasminogen to plasmin [8]. Plasmin mediates invasion directly, by degrading matrix proteins such as collagen IV, fibronectin, and laminin, or indirectly, by activating matrix metalloproteinases MMP-2, -3, and -9 and serine protease uPA [9-12]. uPA exerts its nonproteolytic activity through its interaction with uPA receptor (uPAR), which forms the complex with integrins and controls cell adhesion and cell migration [ PubMed:15180498

Annotations
Experimental Factor Ontology (EFO)
U-937 cell
NCBI Taxonomy Ids
9606
Uberon
lymph node
Cell Ontology (CL)
cardiac muscle cell
MeSH
Cell Nucleus
Disease Ontology (DO)
melanoma

p(HGNC:INS) increases p(HGNC:PLAU)

Modified assertion PubMed:8827475

Annotations
Experimental Factor Ontology (EFO)
LNCAP cell
NCBI Taxonomy Ids
9606
Uberon
muscle tissue
Cell Ontology (CL)
osteoblast
MeSH
Cell Nucleus
Disease Ontology (DO)
cervical cancer
MeSH
Sputum
MeSH
Head and Neck Neoplasms

p(HGNC:FGF1) increases act(p(HGNC:PLAU), ma(cat))

Also, FGFs modulate the expression of uPA receptor on the endothelial cell surface, thus allowing the localization of the proteolytic activity at the leading edge of the cell at the front of migration [22]. Furthermore, FGF1 and FGF2 induce the expression of the plasminogen activator inhibitor (PAI)-1 in cultured endothelial cells leading to a fine modulation of the proteolytic balance [23-25]. PubMed:15863032

Annotations
Experimental Factor Ontology (EFO)
PC-12 cell
NCBI Taxonomy Ids
9606
Uberon
skeletal muscle tissue
Cell Ontology (CL)
megakaryocyte
MeSH
Cell Membrane
Disease Ontology (DO)
neuroblastoma
MeSH
Sputum
MeSH
Head and Neck Neoplasms

p(HGNC:FGF1) increases p(HGNC:PLAU)

The plasmin-plasminogen activator system and matrix metalloproteinases (MMPs) cooperate in this degradation [20]. uPA converts plasminogen into plasmin, a serine protease that degrades fibrin and other matrix proteins, and activate several MMPs, including stromelysin- 1 (MMP-3), collagenase-1 (MMP-1), type IV collagenases (MMP-2 and MMP-9) [21]. FGF1, FGF2, and FGF4 upregulate uPA and MMPs production in endothelial cells. PubMed:15863032

Annotations
Experimental Factor Ontology (EFO)
PC-12 cell
NCBI Taxonomy Ids
9606
Uberon
cardiovascular system endothelium
Cell Ontology (CL)
endothelial cell
MeSH
Cell Membrane
Disease Ontology (DO)
neuroblastoma
MeSH
Sputum
MeSH
Head and Neck Neoplasms

p(HGNC:SPDEF) decreases p(HGNC:PLAU)

Expression of Pdef also results in the down-regulation of urokinase-type plasminogen activator and activation of the promoter of the tumor suppressor gene, MASPIN PubMed:12907642

Annotations
Experimental Factor Ontology (EFO)
LNCAP cell
NCBI Taxonomy Ids
9606
Uberon
prostate gland
Cell Ontology (CL)
epithelial cell
MeSH
Cytoplasm
Disease Ontology (DO)
hematologic cancer

act(p(HGNC:CTSB), ma(cat)) increases act(p(HGNC:PLAU), ma(cat))

uPA is secreted as an inactive single-chain proenzyme. Secreted pro-uPA binds to the uPA receptor (uPAR) present on many different cell types. Cleavage of pro-uPA by plasmin, Factor XIIa or cathepsin B yields the active enzyme consisting of two disulfide-linked chains (17). PubMed:11172729

Annotations
Experimental Factor Ontology (EFO)
293T/17 cell
NCBI Taxonomy Ids
9606
Uberon
endothelium
Cell Ontology (CL)
neutrophil
MeSH
Cell Nucleus
Disease Ontology (DO)
breast cancer

a(CHEBI:progesterone) decreases p(HGNC:PLAU)

Modified assertion PubMed:11566443

Annotations
Experimental Factor Ontology (EFO)
293 cell
NCBI Taxonomy Ids
9606
Uberon
sensory epithelium
Cell Ontology (CL)
fibroblast
MeSH
Cell Nucleus
Disease Ontology (DO)
medulloblastoma

act(p(HGNC:IGF1R), ma(kin)) increases p(HGNC:PLAU)

Modified assertion PubMed:10524682

Annotations
Experimental Factor Ontology (EFO)
HUVEC cell line
NCBI Taxonomy Ids
9606
Uberon
endothelium
Cell Ontology (CL)
chondrocyte
MeSH
Cytoplasm
Disease Ontology (DO)
lung cancer

complex(p(HGNC:PLAU), p(HGNC:PLAUR)) increases act(p(HGNC:PLAU), ma(cat))

uPA-induced monocyte migration was shown to require the interaction of uPAR with integrins [61, 76, 81]. PubMed:11841347

Annotations
Experimental Factor Ontology (EFO)
HUVEC cell line
NCBI Taxonomy Ids
9606
Uberon
blood vessel smooth muscle
Cell Ontology (CL)
endothelial cell of umbilical vein
MeSH
Extracellular Space
Disease Ontology (DO)
atherosclerosis

complex(p(HGNC:PLAU), p(HGNC:PLAUR)) directlyIncreases act(p(HGNC:PLAU), ma(cat))

Upon the binding of prourokinase to uPAR, prourokinase is converted to urokinase, which plays a critical role in initiating cell migration by degrading the extracellular components [14], a process that is essential for cell penetration through the extracellular matrix (ECM) during angiogenesis and tumor metastasis [15,16]. PubMed:15733059

Annotations
Experimental Factor Ontology (EFO)
HeLa cell
NCBI Taxonomy Ids
9606
Uberon
kidney
Cell Ontology (CL)
T cell
MeSH
Cell Nucleus
Disease Ontology (DO)
liver cancer
MeSH
Sputum
MeSH
Head and Neck Neoplasms

complex(p(HGNC:PLAU), p(HGNC:PLAUR)) directlyIncreases act(p(HGNC:PLAU), ma(cat))

(4) the EGF-induced cell migration was statistically higher inAR negative than in AR positive cells with a similar increase with respect to basal value (about 2.6 fold); (5) the Matrigel invasion was statistically higher in AR negative than in AR positive PCa cells also if the increment of Matrigel invasion after EGF treatment was statistically higher in AR positive respect to AR negative cells; (6) the EGF induced uPA secretion and its membrane uptake through the increment of uPAR; PubMed:15886816

Annotations
Experimental Factor Ontology (EFO)
HL-60 cell
NCBI Taxonomy Ids
9606
Uberon
large intestine
Cell Ontology (CL)
muscle cell
MeSH
Cell Membrane
Disease Ontology (DO)
multiple myeloma
MeSH
Sputum
MeSH
Head and Neck Neoplasms

p(HGNC:HOXD3) increases p(HGNC:PLAU)

We have previously established that Hox D3 is required for expression of integrin alphavbeta3 and urokinase plasminogen activator (uPA), which contribute to EC adhesion, invasion, and migration during angiogenesis. PubMed:10648567

Appears in Networks:

p(HGNC:HOXD3) increases p(HGNC:PLAU)

exposure of EC to the angiogenic cytokine bFGF leads to increased levels of Hox D3, resulting in the functional expression of the angiogenic-promoting genes integrin β3 and uPA in these cells Other:9314544

Appears in Networks:

act(p(HGNC:HOXD3), ma(tscript)) increases p(HGNC:PLAU)

Stimulation of EC with basic fibroblast growth factor (bFGF) resulted in increased expression of Hox D3, integrin alphavbeta3, and the urokinase plasminogen activator (uPA). Hox D3 antisense blocked the ability of bFGF to induce uPA and integrin alphavbeta3 expression, yet had no effect on EC cell proliferation or bFGF-mediated cyclin D1 expression. Expression of Hox D3, in the absence of bFGF, resulted in enhanced expression of integrin alphavbeta3 and uPA. Other:9314544

Appears in Networks:

act(p(HGNC:HOXD3), ma(tscript)) increases p(HGNC:PLAU)

uPAR activation by uPA induces its association with platelet-derived growth factor receptor (PDGFR)-beta. The interaction results in PDGF-independent PDGFR-beta activation by phosphorylation of cytoplasmic tyrosine kinase domains and receptor dimerization. Association of the receptors as well as the tyrosine kinase activity of PDGFR-beta are decisive in mediating uPA-induced downstream signaling that regulates Other:15889147

Appears in Networks:

p(HGNC:APP, frag(672_713)) increases p(HGNC:PLAU)

Amyloid beta-protein stimulates the expression of urokinase-type plasminogen activator (uPA) and its receptor (uPAR) in human cerebrovascular smooth muscle cells. PubMed:12754271

Annotations
NCBI Taxonomy Ids
9606
Cell Ontology (CL)
regular cardiac myocyte
NeuroMMSigDB
Plasminogen activator subgraph
NeuroMMSigDB
Amyloidogenic subgraph

a(CHEBI:"amyloid-beta") increases p(HGNC:PLAU)

Amyloid beta-protein stimulates the expression of urokinase-type plasminogen activator (uPA) and its receptor (uPAR) in human cerebrovascular smooth muscle cells. PubMed:12754271

p(HGNC:GSN) directlyIncreases act(p(HGNC:PLAU), ma(tscript))

Although initially regarded as a tumor suppressor, gelsolin expression in certain tumors correlates with poor prognosis and therapy-resistance. In vitro, gelsolin has anti-apoptotic and pro-migratory functions and is critical for invasion of some types of tumor cells PubMed:22927998

Annotations
NCBI Taxonomy Ids
9606
Experimental Factor Ontology (EFO)
Caco-2
Disease Ontology (DO)
colorectal cancer
MeSH
Neoplasms

deg(p(HGNC:GSN)) decreases p(HGNC:PLAU)

Microarray analysis and quantitative PCR indicate that gelsolin overexpression induces the upregulation of invasion-promoting genes in colorectal cancer cells, including the matrix-degrading urokinase-type plasminogen activator (uPA). Conversely, gelsolin knockdown reduces uPA levels, as well as uPA secretion PubMed:22927998

Annotations
NCBI Taxonomy Ids
9606
Experimental Factor Ontology (EFO)
Caco-2
Disease Ontology (DO)
colorectal cancer
MeSH
Neoplasms

deg(p(HGNC:GSN)) decreases tloc(p(HGNC:PLAU), fromLoc(GOCC:intracellular), toLoc(GOCC:"extracellular space"))

Microarray analysis and quantitative PCR indicate that gelsolin overexpression induces the upregulation of invasion-promoting genes in colorectal cancer cells, including the matrix-degrading urokinase-type plasminogen activator (uPA). Conversely, gelsolin knockdown reduces uPA levels, as well as uPA secretion PubMed:22927998

Annotations
NCBI Taxonomy Ids
9606
Experimental Factor Ontology (EFO)
Caco-2
Disease Ontology (DO)
colorectal cancer
MeSH
Neoplasms

p(HGNC:GSN) directlyIncreases act(p(HGNC:PLAU), ma(tscript))

Although initially regarded as a tumor suppressor, gelsolin expression in certain tumors correlates with poor prognosis and therapy-resistance. In vitro, gelsolin has anti-apoptotic and pro-migratory functions and is critical for invasion of some types of tumor cells PubMed:22927998

Annotations
MeSH
Microtubules
Experimental Factor Ontology (EFO)
Caco-2
MeSH
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:GSN)) decreases p(HGNC:PLAU)

Microarray analysis and quantitative PCR indicate that gelsolin overexpression induces the upregulation of invasion-promoting genes in colorectal cancer cells, including the matrix-degrading urokinase-type plasminogen activator (uPA). Conversely, gelsolin knockdown reduces uPA levels, as well as uPA secretion PubMed:22927998

Annotations
MeSH
Microtubules
Experimental Factor Ontology (EFO)
Caco-2
MeSH
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:GSN)) decreases tloc(p(HGNC:PLAU), fromLoc(GOCC:intracellular), toLoc(GOCC:"extracellular space"))

Microarray analysis and quantitative PCR indicate that gelsolin overexpression induces the upregulation of invasion-promoting genes in colorectal cancer cells, including the matrix-degrading urokinase-type plasminogen activator (uPA). Conversely, gelsolin knockdown reduces uPA levels, as well as uPA secretion PubMed:22927998

Annotations
MeSH
Microtubules
Experimental Factor Ontology (EFO)
Caco-2
MeSH
Neoplasms
Evidence and Conclusion Ontology
immunohistochemistry
MeSH
Plasma
NCBI Taxonomy Names
Mus musculus
Disease Ontology (DO)
colorectal cancer
NCBI Taxonomy Ids
9606

p(HGNC:GSN) directlyIncreases act(p(HGNC:PLAU), ma(tscript))

Although initially regarded as a tumor suppressor, gelsolin expression in certain tumors correlates with poor prognosis and therapy-resistance. In vitro, gelsolin has anti-apoptotic and pro-migratory functions and is critical for invasion of some types of tumor cells PubMed:22927998

deg(p(HGNC:GSN)) decreases p(HGNC:PLAU)

Microarray analysis and quantitative PCR indicate that gelsolin overexpression induces the upregulation of invasion-promoting genes in colorectal cancer cells, including the matrix-degrading urokinase-type plasminogen activator (uPA). Conversely, gelsolin knockdown reduces uPA levels, as well as uPA secretion PubMed:22927998

deg(p(HGNC:GSN)) decreases tloc(p(HGNC:PLAU), fromLoc(GOCC:intracellular), toLoc(GOCC:"extracellular space"))

Microarray analysis and quantitative PCR indicate that gelsolin overexpression induces the upregulation of invasion-promoting genes in colorectal cancer cells, including the matrix-degrading urokinase-type plasminogen activator (uPA). Conversely, gelsolin knockdown reduces uPA levels, as well as uPA secretion PubMed:22927998

p(HGNC:GSN) directlyIncreases act(p(HGNC:PLAU), ma(tscript))

Although initially regarded as a tumor suppressor, gelsolin expression in certain tumors correlates with poor prognosis and therapy-resistance. In vitro, gelsolin has anti-apoptotic and pro-migratory functions and is critical for invasion of some types of tumor cells PubMed:22927998

Annotations
Experimental Factor Ontology (EFO)
Caco-2
MeSH
Intracellular Space
MeSH
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:GSN)) decreases p(HGNC:PLAU)

Microarray analysis and quantitative PCR indicate that gelsolin overexpression induces the upregulation of invasion-promoting genes in colorectal cancer cells, including the matrix-degrading urokinase-type plasminogen activator (uPA). Conversely, gelsolin knockdown reduces uPA levels, as well as uPA secretion PubMed:22927998

Annotations
Experimental Factor Ontology (EFO)
Caco-2
MeSH
Intracellular Space
MeSH
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:GSN)) decreases tloc(p(HGNC:PLAU), fromLoc(GOCC:intracellular), toLoc(GOCC:"extracellular space"))

Microarray analysis and quantitative PCR indicate that gelsolin overexpression induces the upregulation of invasion-promoting genes in colorectal cancer cells, including the matrix-degrading urokinase-type plasminogen activator (uPA). Conversely, gelsolin knockdown reduces uPA levels, as well as uPA secretion PubMed:22927998

Annotations
Experimental Factor Ontology (EFO)
Caco-2
MeSH
Intracellular Space
MeSH
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

Out-Edges 47

act(p(HGNC:PLAU), ma(cat)) increases act(p(HGNC:MMP1), ma(cat))

The plasmin-plasminogen activator system and matrix metalloproteinases (MMPs) cooperate in this degradation [20]. uPA converts plasminogen into plasmin, a serine protease that degrades fibrin and other matrix proteins, and activate several MMPs, including stromelysin- 1 (MMP-3), collagenase-1 (MMP-1), type IV collagenases (MMP-2 and MMP-9) [21]. FGF1, FGF2, and FGF4 upregulate uPA and MMPs production in endothelial cells. PubMed:15863032

Annotations
Experimental Factor Ontology (EFO)
PC-12 cell
NCBI Taxonomy Ids
9606
Uberon
cardiovascular system endothelium
Cell Ontology (CL)
endothelial cell
MeSH
Cell Membrane
Disease Ontology (DO)
neuroblastoma
MeSH
Sputum
MeSH
Head and Neck Neoplasms

act(p(HGNC:PLAU), ma(cat)) decreases bp(GOBP:"platelet aggregation")

VEGF increases the expression and activation of the fibrinolytic proteases urokinase and tissue-type plasminogen activator but also induces expression of the prothrombotic components plasminogen activator inhibitor, VWF, and tissue factor PubMed:11350732

Annotations
Experimental Factor Ontology (EFO)
HUVEC cell line
NCBI Taxonomy Ids
9606
Uberon
smooth muscle tissue
Cell Ontology (CL)
platelet
MeSH
Cell Nucleus
Disease Ontology (DO)
lung cancer

act(p(HGNC:PLAU), ma(cat)) increases act(p(HGNC:STAT2), ma(tscript))

In several cell lines uPA activates signal pathways involved in cytoskeleton reorganization: Hsk-kinases, kinases of focal contacts, paxillin, the p130CAS protein, MAP-kinases, the transcription activators STAT1 and STAT2, protein kinase Cepsilon responsible for cytokeratin phosphorylation [48, 50-53]. PubMed:11841347

Annotations
Experimental Factor Ontology (EFO)
Saos-2 cell
NCBI Taxonomy Ids
9606
Uberon
prostate gland
Cell Ontology (CL)
monocyte
MeSH
Extracellular Space
Disease Ontology (DO)
endometrial cancer

act(p(HGNC:PLAU), ma(cat)) increases act(p(SFAM:"SRC Family"), ma(kin))

However, the functions of uPA are not limited to the proteolytic activation of plasmin and of the growth factors on the cell surface. Recently accumulated data suggest that binding of uPA to membrane receptors on certain cells also directly initiates signaling cascades involved in the regulation of cell migration and proliferation independently of the ability of uPA to activate the growth factors. Thus, uPA-induced cell migration is associated with the activation of Janus kinases and of nonreceptor Src-kinases in certain cells [47-49]. PubMed:11841347

Annotations
Experimental Factor Ontology (EFO)
LNCAP cell
NCBI Taxonomy Ids
9606
Uberon
prostate gland
Cell Ontology (CL)
T cell
MeSH
Extracellular Space
Disease Ontology (DO)
endometrial cancer

p(HGNC:PLAU) increases act(p(SFAM:"SRC Family"), ma(kin))

Several studies have indicated that u-PA binding also activates focal adhesion kinase (FAK) [52], protein kinase C (PKC) [53], ERK1/2 [38], Janus associated kinases (JAK) [54,55], src family tyrosine kinases [56], and G-proteins [57]. PubMed:16611153

Annotations
Experimental Factor Ontology (EFO)
THP-1 cell
NCBI Taxonomy Ids
9606
Uberon
aorta
Cell Ontology (CL)
smooth muscle cell
MeSH
Golgi Apparatus
Disease Ontology (DO)
breast cancer
MeSH
Sputum
MeSH
Head and Neck Neoplasms

act(p(HGNC:PLAU), ma(cat)) increases act(p(HGNC:PRKCE), ma(kin))

In several cell lines uPA activates signal pathways involved in cytoskeleton reorganization: Hsk-kinases, kinases of focal contacts, paxillin, the p130CAS protein, MAP-kinases, the transcription activators STAT1 and STAT2, protein kinase Cepsilon responsible for cytokeratin phosphorylation [48, 50-53]. PubMed:11841347

Annotations
Experimental Factor Ontology (EFO)
Saos-2 cell
NCBI Taxonomy Ids
9606
Uberon
prostate gland
Cell Ontology (CL)
monocyte
MeSH
Extracellular Space
Disease Ontology (DO)
endometrial cancer

act(p(HGNC:PLAU), ma(cat)) increases act(p(HGNC:MMP9), ma(cat))

The plasmin-plasminogen activator system and matrix metalloproteinases (MMPs) cooperate in this degradation [20]. uPA converts plasminogen into plasmin, a serine protease that degrades fibrin and other matrix proteins, and activate several MMPs, including stromelysin- 1 (MMP-3), collagenase-1 (MMP-1), type IV collagenases (MMP-2 and MMP-9) [21]. FGF1, FGF2, and FGF4 upregulate uPA and MMPs production in endothelial cells. PubMed:15863032

Annotations
Experimental Factor Ontology (EFO)
PC-12 cell
NCBI Taxonomy Ids
9606
Uberon
cardiovascular system endothelium
Cell Ontology (CL)
endothelial cell
MeSH
Cell Membrane
Disease Ontology (DO)
neuroblastoma
MeSH
Sputum
MeSH
Head and Neck Neoplasms

p(HGNC:PLAU) increases a(CHEBI:"reactive oxygen species")

uPA increases ROS production in SMCs by stimulating both the expression and activity of NAD(P)H oxidases (Nox1 and Nox4, equally) (Menshikov et al. 2006b). PubMed:19064999

Annotations
Experimental Factor Ontology (EFO)
THP-1 cell
NCBI Taxonomy Ids
9606
Uberon
bone marrow
Cell Ontology (CL)
smooth muscle cell
MeSH
Extracellular Matrix
Disease Ontology (DO)
lung cancer
MeSH
Sputum
MeSH
Head and Neck Neoplasms

act(p(HGNC:PLAU), ma(cat)) increases bp(GOBP:"monocyte extravasation")

uPA-induced monocyte migration was shown to require the interaction of uPAR with integrins [61, 76, 81]. PubMed:11841347

Annotations
Experimental Factor Ontology (EFO)
HUVEC cell line
NCBI Taxonomy Ids
9606
Uberon
blood vessel smooth muscle
Cell Ontology (CL)
endothelial cell of umbilical vein
MeSH
Extracellular Space
Disease Ontology (DO)
atherosclerosis

p(HGNC:PLAU) increases act(p(HGNC:PLAUR), ma(cat))

In human coronary artery vascular smooth muscle cells, UPA stimulates cell migration via a UPA receptor (UPAR, or PLAUR; 173391) signaling complex containing TYK2 (176941) and phosphatidylinositol 3-kinase (PI3K; see 601232). Kiian et al. (2003) showed that association of TYK2 and PI3K with active GTP-bound forms of both RHOA (ARHA; 165390) and RAC1 (602048), but not CDC42 (116952), as well as phosphorylation of myosin light chain (see 160781), are downstream events required for UPA/UPAR-directed migration. Online Resource:OMIM text for PLAU

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

p(HGNC:PLAU) increases act(p(HGNC:PLAUR), ma(cat))

Several molecular interactions between the matrix metalloproteinase (MMP) and the plasminogen/plasmin (fibrinolytic) system may affect cellular fibrinolysis. MMP-3 (stromelysin-1) specifically hydrolyzes urokinase (u-PA), yielding a 17 kD NH2-terminal fragment containing the functionally intact receptor (u-PAR)-binding sequence and a 32 kD COOH-terminal fragment containing the intact serine proteinase domain. PubMed:11841344

Annotations
Experimental Factor Ontology (EFO)
LNCAP cell
NCBI Taxonomy Ids
9606
Uberon
prostate gland
Cell Ontology (CL)
T cell
MeSH
Extracellular Space
Disease Ontology (DO)
endometrial cancer

p(HGNC:PLAU) increases tloc(p(HGNC:PLAUR), fromLoc(GOCC:intracellular), toLoc(GOCC:"cell surface"))

Expression of p53 protein in p53(-/-) cells suppressed basal and urokinase (uPA)-induced cell surface uPAR protein and increased uPAR mRNA degradation. a novel regulatory role for p53 as a uPAR mRNA binding protein that down-regulates uPAR expression, destabilizes uPAR mRNA, and thereby contributes to the viability of human airway epithelial or lung carcinoma cells. PubMed:17548471

Annotations
Experimental Factor Ontology (EFO)
NCI-H1299 cell
NCBI Taxonomy Ids
9606
Uberon
heart
Cell Ontology (CL)
fat cell
MeSH
Cell Nucleus
Disease Ontology (DO)
osteosarcoma
MeSH
Sputum
MeSH
Head and Neck Neoplasms

act(p(HGNC:PLAU), ma(cat)) increases act(p(SFAM:"JAK Family"), ma(kin))

However, the functions of uPA are not limited to the proteolytic activation of plasmin and of the growth factors on the cell surface. Recently accumulated data suggest that binding of uPA to membrane receptors on certain cells also directly initiates signaling cascades involved in the regulation of cell migration and proliferation independently of the ability of uPA to activate the growth factors. Thus, uPA-induced cell migration is associated with the activation of Janus kinases and of nonreceptor Src-kinases in certain cells [47-49]. PubMed:11841347

Annotations
Experimental Factor Ontology (EFO)
LNCAP cell
NCBI Taxonomy Ids
9606
Uberon
prostate gland
Cell Ontology (CL)
T cell
MeSH
Extracellular Space
Disease Ontology (DO)
endometrial cancer

p(HGNC:PLAU) increases act(p(SFAM:"JAK Family"), ma(kin))

Several studies have indicated that u-PA binding also activates focal adhesion kinase (FAK) [52], protein kinase C (PKC) [53], ERK1/2 [38], Janus associated kinases (JAK) [54,55], src family tyrosine kinases [56], and G-proteins [57]. PubMed:16611153

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

p(HGNC:PLAU) increases act(p(SFAM:"JAK Family"), ma(kin))

Dumler, I., Kopmann, A., Weis, A., Mayboroda, O.A., Wagner, K., Gulba, D.C., and Haller, H. 1999a. Urokinase activates the Jak/ Stat signal transduction pathway in human vascular endothelial cells. Arterioscler. Thromb. Vasc. Biol. 19: 290–297. PMID:9974409. PubMed:19064999

Annotations
Experimental Factor Ontology (EFO)
MCF7 cell
NCBI Taxonomy Ids
9606
Uberon
cardiovascular system
Cell Ontology (CL)
endothelial cell
MeSH
Extracellular Matrix
Disease Ontology (DO)
lung cancer
MeSH
Sputum
MeSH
Head and Neck Neoplasms

act(p(HGNC:PLAU), ma(cat)) increases act(p(HGNC:NOX1), ma(cat))

uPA increases ROS production in SMCs by stimulating both the expression and activity of NAD(P)H oxidases (Nox1 and Nox4, equally) (Menshikov et al. 2006b). PubMed:19064999

Annotations
Experimental Factor Ontology (EFO)
THP-1 cell
NCBI Taxonomy Ids
9606
Uberon
bone marrow
Cell Ontology (CL)
smooth muscle cell
MeSH
Extracellular Matrix
Disease Ontology (DO)
lung cancer
MeSH
Sputum
MeSH
Head and Neck Neoplasms

p(HGNC:PLAU) increases a(CHEBI:icosanoid)

Menshikov, M., Torosyan, N., Elizarova, E., Plakida, K., Vorotnikov, A., Parfyonova, Y., et al. 2006b. Urokinase induces matrix metalloproteinase-9/gelatinase B expression in THP-1 monocytes via ERK1/2 and cytosolic phospholipase A2 activation and eicosanoid production. J. Vasc. Res. 43: 482–490. doi:10. 1159/000095248. PMID:16926552. PubMed:19064999

Annotations
Experimental Factor Ontology (EFO)
THP-1 cell
NCBI Taxonomy Ids
9606
Uberon
aorta
Cell Ontology (CL)
smooth muscle cell
MeSH
Extracellular Matrix
Disease Ontology (DO)
lung cancer
MeSH
Sputum
MeSH
Head and Neck Neoplasms

p(HGNC:PLAU) increases act(p(HGNC:MAPK1), ma(kin))

Menshikov, M., Torosyan, N., Elizarova, E., Plakida, K., Vorotnikov, A., Parfyonova, Y., et al. 2006b. Urokinase induces matrix metalloproteinase-9/gelatinase B expression in THP-1 monocytes via ERK1/2 and cytosolic phospholipase A2 activation and eicosanoid production. J. Vasc. Res. 43: 482–490. doi:10. 1159/000095248. PMID:16926552. PubMed:19064999

Annotations
Experimental Factor Ontology (EFO)
THP-1 cell
NCBI Taxonomy Ids
9606
Uberon
aorta
Cell Ontology (CL)
smooth muscle cell
MeSH
Extracellular Matrix
Disease Ontology (DO)
lung cancer
MeSH
Sputum
MeSH
Head and Neck Neoplasms

p(HGNC:PLAU) increases tloc(a(SCHEM:Superoxides), fromLoc(GOCC:intracellular), toLoc(GOCC:"extracellular space"))

It was reported that uPA contributes to superoxide production (Cao et al. 1995) and release (Sitrin et al. 2000) by neutrophils. PubMed:19064999

Annotations
Experimental Factor Ontology (EFO)
MCF7 cell
NCBI Taxonomy Ids
9606
Uberon
cardiovascular system
Cell Ontology (CL)
neutrophil
MeSH
Extracellular Matrix
Disease Ontology (DO)
lung cancer
MeSH
Sputum
MeSH
Head and Neck Neoplasms

p(HGNC:PLAU) increases path(MESHD:Atherosclerosis)

This is further supported by in vivo studies demonstrating that overexpression of u-PA in macrophages, accelerates atherosclerotic progression and early death in these transgenic mice [200]. PubMed:16611153

Annotations
Experimental Factor Ontology (EFO)
THP-1 cell
NCBI Taxonomy Ids
9606
Uberon
aorta
Cell Ontology (CL)
macrophage
MeSH
Golgi Apparatus
Disease Ontology (DO)
breast cancer
MeSH
Sputum
MeSH
Head and Neck Neoplasms

p(HGNC:PLAU) increases bp(GOBP:"mitotic nuclear division")

However, the mitogenic effect of urokinase on certain cells such as prostate cancer cells (PC3), human glomerular epithelial cells, osteoblasts was found to be mediated simply via uPAR occupancy and does not require its catalytic activity [82, 83]. PubMed:11841347

Annotations
Experimental Factor Ontology (EFO)
LNCAP cell
NCBI Taxonomy Ids
9606
Uberon
prostate gland
Cell Ontology (CL)
T cell
MeSH
Extracellular Space
Disease Ontology (DO)
endometrial cancer

act(p(HGNC:PLAU), ma(cat)) increases bp(GOBP:"mitotic nuclear division")

The involvement of urokinase in tissue morphogenesis is also due to its ability to stimulate the cell proliferation. A mitogenic effect of uPA has been shown for various cells; however, its mechanism remains unclear in detail and seems to vary depending on the cell type. It was originally conceived that uPA can affect mitogenesis by a direct proteolytic- or plasmin-mediated activation of latent growth factors, such as HGF, bFGF, and TGF-beta [42-45]. PubMed:11841347

Annotations
Experimental Factor Ontology (EFO)
Saos-2 cell
NCBI Taxonomy Ids
9606
Uberon
blood vessel smooth muscle
Cell Ontology (CL)
endothelial cell
MeSH
Extracellular Space
Disease Ontology (DO)
atherosclerosis

act(p(HGNC:PLAU), ma(cat)) increases p(HGNC:MST1)

The main role of uPA in extracellular proteolysis is a generation of cell surface associated plasmin cleaving the main components of the basement membrane and of the extracellular matrix and activating matrix metalloproteinases, which degrade the components resistant to plasmin [1, 3, 42]. Essential for the proteolytic function of uPA is its ability to directly or via plasmin production activate latent or release matrix-bound growth factors. Thus, uPA itself proteolytically activates proforms of hepatocyte growth factor (HGF), of macrophage-stimulating protein (MSP), and of an isoform of vascular endothelial growth factor (VEGF189) [43, 44]. PubMed:11841347

Annotations
Experimental Factor Ontology (EFO)
Saos-2 cell
NCBI Taxonomy Ids
9606
Uberon
blood vessel smooth muscle
Cell Ontology (CL)
endothelial cell
MeSH
Extracellular Space
Disease Ontology (DO)
atherosclerosis

act(p(HGNC:PLAU), ma(cat)) increases p(HGNC:TGFB1)

The involvement of urokinase in tissue morphogenesis is also due to its ability to stimulate the cell proliferation. A mitogenic effect of uPA has been shown for various cells; however, its mechanism remains unclear in detail and seems to vary depending on the cell type. It was originally conceived that uPA can affect mitogenesis by a direct proteolytic- or plasmin-mediated activation of latent growth factors, such as HGF, bFGF, and TGF-beta [42-45]. PubMed:11841347

Annotations
Experimental Factor Ontology (EFO)
Saos-2 cell
NCBI Taxonomy Ids
9606
Uberon
blood vessel smooth muscle
Cell Ontology (CL)
endothelial cell
MeSH
Extracellular Space
Disease Ontology (DO)
atherosclerosis

act(p(HGNC:PLAU), ma(cat)) increases bp(GOBP:"DNA replication")

PAs mitogenic stimulation of serum-starved cells was associated with the internalization of their molecules PubMed:10801075

Annotations
Experimental Factor Ontology (EFO)
U-937 cell
NCBI Taxonomy Ids
9606
Uberon
adipose tissue
Cell Ontology (CL)
neuron
MeSH
Cell Membrane
Disease Ontology (DO)
breast cancer

act(p(HGNC:PLAU), ma(cat)) increases bp(GOBP:"DNA replication")

upon stimulation with mitogens (fetal calf serum (FCS), u-PA, t-PA) the cyclin A mRNA expression was observed in concomitance with the activation of DNA synthesis. PubMed:10801075

Annotations
Experimental Factor Ontology (EFO)
U-937 cell
NCBI Taxonomy Ids
9606
Uberon
adipose tissue
Cell Ontology (CL)
neuron
MeSH
Cell Membrane
Disease Ontology (DO)
breast cancer

act(p(HGNC:PLAU), ma(cat)) increases bp(GOBP:"DNA replication")

To stimulate proliferation of human fibroblasts, human kidney cells, and mesothelial cells, the interaction of uPA with uPAR and its proteolytic activity is necessary, although the effect of urokinase in these cases is not mediated by plasminogen activation [84-86]. In our laboratory, it was shown that a catalytically active uPA and plasmin generation were required for the stimulation of DNA synthesis in vascular SMC [87]. PubMed:11841347

Annotations
Experimental Factor Ontology (EFO)
Saos-2 cell
NCBI Taxonomy Ids
9606
Uberon
blood vessel smooth muscle
Cell Ontology (CL)
endothelial cell
MeSH
Extracellular Space
Disease Ontology (DO)
atherosclerosis

act(p(HGNC:PLAU), ma(cat)) increases bp(GOBP:"DNA replication")

In vascular SMCs, uPA proteolytic activity and uPA-dependent plasmin generation were required for stimulation of DNA synthesis (Stepanova et al. 1999). PubMed:19064999

Annotations
Experimental Factor Ontology (EFO)
MCF7 cell
NCBI Taxonomy Ids
9606
Uberon
cardiovascular system
Cell Ontology (CL)
smooth muscle cell
MeSH
Extracellular Matrix
Disease Ontology (DO)
lung cancer
MeSH
Sputum
MeSH
Head and Neck Neoplasms

act(p(HGNC:PLAU), ma(cat)) increases path(SDIS:"basophil extravasation")

Thus, uPA is a potent chemoattractant for basophils that seems to act through exposure of the chemotactic uPAR epitope uPAR84-95, which is an endogenous ligand for FPRL2 and FPRL1. PubMed:15494526

Annotations
Experimental Factor Ontology (EFO)
293 cell
NCBI Taxonomy Ids
9606
Uberon
endometrium
Cell Ontology (CL)
cardiac muscle cell
MeSH
Cytoplasm
Disease Ontology (DO)
melanoma
MeSH
Hypercholesterolemia

act(p(HGNC:PLAU), ma(cat)) increases bp(GOBP:"JAK-STAT cascade")

However, the functions of uPA are not limited to the proteolytic activation of plasmin and of the growth factors on the cell surface. Recently accumulated data suggest that binding of uPA to membrane receptors on certain cells also directly initiates signaling cascades involved in the regulation of cell migration and proliferation independently of the ability of uPA to activate the growth factors. Thus, uPA-induced cell migration is associated with the activation of Janus kinases and of nonreceptor Src-kinases in certain cells [47-49]. PubMed:11841347

Annotations
Experimental Factor Ontology (EFO)
LNCAP cell
NCBI Taxonomy Ids
9606
Uberon
prostate gland
Cell Ontology (CL)
T cell
MeSH
Extracellular Space
Disease Ontology (DO)
endometrial cancer

tloc(p(HGNC:PLAU), fromLoc(GOCCID:0005886), toLoc(GOCCID:0005737)) increases act(p(HGNC:PLAU), ma(cat))

PAs mitogenic stimulation of serum-starved cells was associated with the internalization of their molecules PubMed:10801075

Annotations
Experimental Factor Ontology (EFO)
U-937 cell
NCBI Taxonomy Ids
9606
Uberon
adipose tissue
Cell Ontology (CL)
neuron
MeSH
Cell Membrane
Disease Ontology (DO)
breast cancer

act(p(HGNC:PLAU), ma(cat)) increases p(HGNC:BCAR1)

In several cell lines uPA activates signal pathways involved in cytoskeleton reorganization: Hsk-kinases, kinases of focal contacts, paxillin, the p130CAS protein, MAP-kinases, the transcription activators STAT1 and STAT2, protein kinase Cepsilon responsible for cytokeratin phosphorylation [48, 50-53]. PubMed:11841347

Annotations
Experimental Factor Ontology (EFO)
Saos-2 cell
NCBI Taxonomy Ids
9606
Uberon
prostate gland
Cell Ontology (CL)
monocyte
MeSH
Extracellular Space
Disease Ontology (DO)
endometrial cancer

act(p(HGNC:PLAU), ma(cat)) increases act(p(SFAM:"MAPK Erk1/2 Family"), ma(kin))

In several cell lines uPA activates signal pathways involved in cytoskeleton reorganization: Hsk-kinases, kinases of focal contacts, paxillin, the p130CAS protein, MAP-kinases, the transcription activators STAT1 and STAT2, protein kinase Cepsilon responsible for cytokeratin phosphorylation [48, 50-53]. PubMed:11841347

Annotations
Experimental Factor Ontology (EFO)
Saos-2 cell
NCBI Taxonomy Ids
9606
Uberon
prostate gland
Cell Ontology (CL)
monocyte
MeSH
Extracellular Space
Disease Ontology (DO)
endometrial cancer

act(p(HGNC:PLAU), ma(cat)) increases act(p(SFAM:"PRKC Family"), ma(kin))

In this study, the down-regulation of the uPAR expression seemed to inhibit signaling pathways depending on the uPA proteolytic activity and also on the binding to the uPAR. The uPA catalytic activity seemed to activate protein kinase C through the matrix destruction and the disruption of integrin ligation, whereas the uPAR occupation activated the MAP-kinase pathway. PubMed:11841347

Annotations
Experimental Factor Ontology (EFO)
Saos-2 cell
NCBI Taxonomy Ids
9606
Uberon
prostate gland
Cell Ontology (CL)
monocyte
MeSH
Extracellular Space
Disease Ontology (DO)
endometrial cancer

act(p(HGNC:PLAU), ma(cat)) increases act(p(HGNC:NOX4), ma(cat))

uPA increases ROS production in SMCs by stimulating both the expression and activity of NAD(P)H oxidases (Nox1 and Nox4, equally) (Menshikov et al. 2006b). PubMed:19064999

Annotations
Experimental Factor Ontology (EFO)
THP-1 cell
NCBI Taxonomy Ids
9606
Uberon
bone marrow
Cell Ontology (CL)
smooth muscle cell
MeSH
Extracellular Matrix
Disease Ontology (DO)
lung cancer
MeSH
Sputum
MeSH
Head and Neck Neoplasms

act(p(HGNC:PLAU), ma(cat)) increases act(p(SFAM:"MMP Family"), ma(cat))

Both uPA itself and uPA-generated plasmin can activate the latent matrix metalloproteinases and elastase [46, 148], which are responsible for the subsequent degradation of the extracellular matrix, during the endothelial cell migration and invasion. Moreover these two proteases activate virtually all growth factors involved in angiogenesis [42-45, 147, 149]. Hypoxia has been shown to increase the expression of angiogenic growth factors, but uPA and plasmin are required to provide proteolytic activation of the latent forms or release of matrix-bound growth factors. PubMed:11841347

Annotations
Experimental Factor Ontology (EFO)
LNCAP cell
NCBI Taxonomy Ids
9606
Uberon
prostate gland
Cell Ontology (CL)
T cell
MeSH
Extracellular Space
Disease Ontology (DO)
endometrial cancer

act(p(HGNC:PLAU), ma(cat)) increases act(p(SFAM:"MMP Family"), ma(cat))

PHBP activates scuPA to tcuPA, tcuPA activates matrix metalloproteases (MMPs) and activated MMPs degrade ECM for the tissue remodeling after hepatic injury. PubMed:15320789

Annotations
Experimental Factor Ontology (EFO)
293 cell
NCBI Taxonomy Ids
9606
Uberon
duodenum
Cell Ontology (CL)
hepatocyte
MeSH
Cell Nucleus
Disease Ontology (DO)
gastric adenocarcinoma

act(p(HGNC:PLAU), ma(cat)) directlyIncreases complex(p(HGNC:PDGFRB), p(HGNC:PLAUR))

Urokinase-induced signaling in human vascular smooth muscle cells is mediated by PDGFR-beta.We provide evidence that uPAR activation by uPA induces its association with platelet-derived growth factor receptor (PDGFR)-beta. The interaction results in PDGF-independent PDGFR-beta activation by phosphorylation of cytoplasmic tyrosine kinase domains and receptor dimerization. PubMed:15889147

Appears in Networks:

p(HGNC:PLAU) increases act(p(HGNC:PDGFRB), ma(kin))

Kiyan, J., Kiyan, R., Haller, H., and Dumler, I. 2005. Urokinase-induced signaling in human vascular smooth muscle cells is mediated by PDGFR-beta. EMBO J. 24: 1787–1797. doi:10. 1038/sj.emboj.7600669. PMID:15889147 PubMed:19064999

Appears in Networks:

p(HGNC:PLAU) increases path(MESHD:"Cerebral Hemorrhage")

This suggests that a similar prolonged effect in vivo in the cerebral vessel wall may contribute to loss of integrity and cerebral hemorrhage in CAA. PubMed:12754271

p(HGNC:PLAU) increases deg(p(HGNC:APP, frag(672_713)))

This suggests that increased expression of uPA may initially serve as a protective mechanism leading to localized degradation and clearance of the pathogenic stimulus A beta. PubMed:12754271

p(HGNC:PLAU) increases bp(GOBP:"beta-amyloid clearance")

This suggests that increased expression of uPA may initially serve as a protective mechanism leading to localized degradation and clearance of the pathogenic stimulus A beta. PubMed:12754271

deg(p(HGNC:PLAU)) decreases path(MESHD:"Neoplasm Invasiveness")

The enhanced invasiveness of gelsolin-overexpressing cells was attenuated by treatment with function-blocking antibodies to either uPA or its receptor uPAR, indicating that uPA/uPAR activity is crucial for gelsolin-dependent invasion. PubMed:22927998

Annotations
NCBI Taxonomy Ids
9606
Experimental Factor Ontology (EFO)
Caco-2
Disease Ontology (DO)
colorectal cancer
MeSH
Neoplasms

deg(p(HGNC:PLAU)) decreases path(MESHD:"Neoplasm Invasiveness")

The enhanced invasiveness of gelsolin-overexpressing cells was attenuated by treatment with function-blocking antibodies to either uPA or its receptor uPAR, indicating that uPA/uPAR activity is crucial for gelsolin-dependent invasion. PubMed:22927998

Annotations
MeSH
Microtubules
Experimental Factor Ontology (EFO)
Caco-2
MeSH
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:PLAU)) decreases path(MESHD:"Neoplasm Invasiveness")

The enhanced invasiveness of gelsolin-overexpressing cells was attenuated by treatment with function-blocking antibodies to either uPA or its receptor uPAR, indicating that uPA/uPAR activity is crucial for gelsolin-dependent invasion. PubMed:22927998

deg(p(HGNC:PLAU)) decreases path(MESHD:"Neoplasm Invasiveness")

The enhanced invasiveness of gelsolin-overexpressing cells was attenuated by treatment with function-blocking antibodies to either uPA or its receptor uPAR, indicating that uPA/uPAR activity is crucial for gelsolin-dependent invasion. PubMed:22927998

Annotations
Experimental Factor Ontology (EFO)
Caco-2
MeSH
Intracellular Space
MeSH
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

About

BEL Commons is developed and maintained in an academic capacity by Charles Tapley Hoyt and Daniel Domingo-Fernández at the Fraunhofer SCAI Department of Bioinformatics with support from the IMI project, AETIONOMY. It is built on top of the open source project, PyBEL. Please feel free to contact us here to give us feedback or report any issues.