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p(HGNC:SYK)

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Entity

Name
SYK
Namespace
hgnc
Namespace Version
20180906
Namespace URL
https://raw.githubusercontent.com/pharmacome/terminology/b46b65c3da259b6e86026514dfececab7c22a11b/external/hgnc-names.belns

Appears in Networks 7

Tau Modifications v1.9.5

Tau Modifications Sections of NESTOR

Activation and regulation of the inflammasomes v1.0.0

The Spleen Tyrosine Kinase (Syk) Regulates Alzheimer Amyloid-β Production and Tau Hyperphosphorylation* v1.0.0

Caenorhabditis elegans models of tauopathy v1.0.0

Alzheimer's disease pathological lesions activate the spleen tyrosine kinase. v1.0.0

Tau in physiology and pathology v1.0.0

Heme Curation v0.0.1-dev

Mechanistic knowledge surrounding heme

In-Edges 23

a(HBP:"BAY61-3606") directlyDecreases act(p(HGNC:SYK)) View Subject | View Object

We observed that pharmacological inhibition of Syk with BAY61-3606 stimulates Ser-9 phosphorylation of GSK3β in SH-SY5Y cells (Fig. 9, A and B) suggesting that blocking Syk activity results in GSK3β inhibition. PubMed:25331948

Appears in Networks:

act(p(HGNC:GSK3B), ma(kin)) positiveCorrelation act(p(HGNC:SYK)) View Subject | View Object

We observed that pharmacological inhibition of Syk with BAY61-3606 stimulates Ser-9 phosphorylation of GSK3β in SH-SY5Y cells (Fig. 9, A and B) suggesting that blocking Syk activity results in GSK3β inhibition. PubMed:25331948

Appears in Networks:

p(HGNC:GSK3B, pmod(Ph, Ser, 9)) negativeCorrelation act(p(HGNC:SYK)) View Subject | View Object

We observed that pharmacological inhibition of Syk with BAY61-3606 stimulates Ser-9 phosphorylation of GSK3β in SH-SY5Y cells (Fig. 9, A and B) suggesting that blocking Syk activity results in GSK3β inhibition. PubMed:25331948

Appears in Networks:

act(p(HGNC:CLEC7A)) increases act(p(HGNC:SYK)) View Subject | View Object

For example, following sensing of fungal components by the PRR dectin 1 that is expressed on human dendritic cells, signalling via the kinase SYK leads to the formation of a complex that is composed of caspase 8 and mucosa-associated lymphoid tissue lymphoma translocation protein 1 (MALT1); this complex binds to ASC, which possibly recruits cleavage substrates53. The MALT1-ASC-caspase 8 complex directly mediates IL-1β maturation53. PubMed:23702978

Appears in Networks:
Annotations
Confidence
High
NeuroMMSigDB
Caspase subgraph
NeuroMMSigDB
Interleukin signaling subgraph

a(CHEBI:"2-[[7-(3,4-dimethoxyphenyl)-5-imidazo[1,2-c]pyrimidinyl]amino]-3-pyridinecarboxamide") decreases act(p(HGNC:SYK)) View Subject | View Object

The Syk inhibitor BAY61-3606 was used as a positive control in the Syk activity assay, and a dose-dependent inhibition of Syk activity was observed with BAY61-3606 as expected (Fig. 5B). PubMed:25331948

Appears in Networks:

a(CHEBI:"2-[[7-(3,4-dimethoxyphenyl)-5-imidazo[1,2-c]pyrimidinyl]amino]-3-pyridinecarboxamide") decreases act(p(HGNC:SYK)) View Subject | View Object

We found that, like (-)-nilvadipine, Syk inhibition with the selective Syk inhibitor BAY61-3606 resulted in decreased sAPPβ secretion, BACE-1 mRNA, and BACE-1 protein expression (data not shown). PubMed:25331948

Appears in Networks:

complex(a(CHEBI:Nilvadipine), p(HGNC:SYK)) hasComponent p(HGNC:SYK) View Subject | View Object

Appears in Networks:

a(CHEBI:"phorbol 13-acetate 12-myristate") increases act(p(HGNC:SYK)) View Subject | View Object

Tyrosine kinases, including Syk and Bruton’s tyrosine kinase (BTK), are activated following PMA treatment (49, 50), act upstream of RAS/RAF (51, 52), and mediate the activation of the NFkB pathway (53). PubMed:25331948

Appears in Networks:

a(CHEBI:Nilvadipine) decreases act(p(HGNC:SYK)) View Subject | View Object

Using a cell-free assay using human recombinant Syk, we observed that (-)-nilvadipine dose-dependently inhibits Syk activity (Fig. 5A) PubMed:25331948

Appears in Networks:

a(HBP:"Tau aggregates") association p(HGNC:SYK) View Subject | View Object

Most importantly, pathological tau species clearly colo- calize with pSyk (Y525/526) in hippocampal neurons (Fig. 4b). PubMed:28877763

Appears in Networks:
Annotations
Cell Ontology (CL)
hippocampal neuron

a(HBP:"Tau aggregates") association p(HGNC:SYK) View Subject | View Object

We observed a colocalization between pSyk and pTau (S202) immuno- reactivities in cortical neurons. PubMed:28877763

Appears in Networks:
Annotations
Cell Ontology (CL)
cerebral cortex neuron

a(HBP:"Tau aggregates") positiveCorrelation p(HGNC:SYK) View Subject | View Object

In general, we found that neurons that exhibit a high level of pSyk immunoreactivity also demonstrate a higher level of tau pathogenic species whereas neurons that are weakly immunopositive for pSyk show less tau pathology (Figs. 9, 10, 11, 12 and 13). PubMed:28877763

Appears in Networks:
Annotations
MeSH
Neurons

a(HBP:"amyloid-beta aggregates") positiveCorrelation act(p(HGNC:SYK)) View Subject | View Object

In addition, we observed that pSyk immunoreactivity is upregulated near A β plaques but neither colocalizes with microglia nor astrocytes suggesting that it could be of neuronal origin. (Fig. 1e). PubMed:28877763

Appears in Networks:
Annotations
MeSH
Brain
MeSH
Alzheimer Disease

a(HBP:"amyloid-beta aggregates") positiveCorrelation act(p(HGNC:SYK)) View Subject | View Object

In conclusion, activated Syk is not only found in microglia but also in neurons near A β deposits, par- ticularly in dystrophic neurites of Tg APPsw and Tg PS1/APPsw mice supporting a possible role of Syk activation in the formation of dystrophic neurites. PubMed:28877763

Appears in Networks:
Annotations
MeSH
Neurites
MeSH
Neurons

a(HBP:"amyloid-beta aggregates") positiveCorrelation act(p(HGNC:SYK)) View Subject | View Object

We found an increase in Syk activation in DNs surrounding A β deposits as well as in neurons displaying an accumu- lation of phosphorylated Tau at Y18 and elevated levels of MC1 pathogenic tau conformers in AD brain sections whereas only weak immunoreactivity for pSyk was ob- served in brain sections from a non-demented control (Figs. 15, 16 and 17). PubMed:28877763

Appears in Networks:
Annotations
MeSH
Neurites
MeSH
Brain
MeSH
Alzheimer Disease

bp(GO:"microglial cell activation") positiveCorrelation act(p(HGNC:SYK)) View Subject | View Object

To investigate whether pathological Syk activation oc- curs in the brain of AD mouse models, we analyzed the brains of 116-week-old wild-type, Tg APPsw and Tg PS1/APPsw mice using high-resolution confocal micros- copy and immunofluorescence. All transgenic mice (Fig. 1b-e) exhibit an increased Iba-1 and GFAP reactiv- ity compared to wild-type littermates (Fig. 1a). Moreo- ver,wild-type some of the activated amoeboid microglia that are observed in transgenic mice are also strongly positive for pSyk (Fig. 1b-d). PubMed:28877763

Appears in Networks:
Annotations
MeSH
Brain
MeSH
Alzheimer Disease

bp(GO:aging) increases p(HGNC:SYK) View Subject | View Object

In contrast, microscopic fields of older Tg APPsw mice containing A β deposits exhibit a strong increase in pSyk burden (799.95 ± 130.19%) com- pared to age-matched WT mice. PubMed:28877763

Appears in Networks:
Annotations
MeSH
Alzheimer Disease

bp(GO:aging) increases p(HGNC:SYK) View Subject | View Object

Cortical neurons of Tg Tau P301S mice also show an in- crease in tau hyperphosphorylation and pSyk with age (Fig. 7). PubMed:28877763

Appears in Networks:
Annotations
Cell Ontology (CL)
cerebral cortex neuron

p(HGNC:MAPT, pmod(HBP:hyperphosphorylation)) association act(p(HGNC:SYK)) View Subject | View Object

Abnormal Syk activation seems to fol- low tau hyperphosphorylation (S202) in the hippocampus of Tg P301S mice (Fig. 6), as well as the formation of MC1-tau pathological conformers (data not shown here but MC1 and pSyk colocalization were quantified below). PubMed:28877763

Appears in Networks:
Annotations
MeSH
Hippocampus

p(HGNC:MAPT, pmod(HBP:misfolded)) positiveCorrelation act(p(HGNC:SYK)) View Subject | View Object

We found an increase in Syk activation in DNs surrounding A β deposits as well as in neurons displaying an accumu- lation of phosphorylated Tau at Y18 and elevated levels of MC1 pathogenic tau conformers in AD brain sections whereas only weak immunoreactivity for pSyk was ob- served in brain sections from a non-demented control (Figs. 15, 16 and 17). PubMed:28877763

Appears in Networks:
Annotations
MeSH
Neurites
MeSH
Brain
MeSH
Alzheimer Disease

p(HGNC:MAPT, pmod(Ph, Tyr, 18)) positiveCorrelation p(HGNC:SYK) View Subject | View Object

We found that tau phosphorylation at Y18 is significantly increased in neurons that are also immunopositive for pSyk (Fig. 10d, p < 0.05) which is consistent with previous data showing that in vitro Syk can phosphorylates tau at Y18. PubMed:28877763

Appears in Networks:
Annotations
MeSH
Neurons

p(HGNC:MAPT, pmod(Ph, Tyr, 18)) increases act(p(HGNC:SYK)) View Subject | View Object

Altogether, these data suggest that only certain pathogenic forms of tau (MC1, Y18) promote Syk activation, whereas Syk activation appears to directly in- duce tau phosphorylation at Y18 and to indirectly regulate tau phosphorylation at multiple epitopes (S396/404, S202) as well as tau misfolding (MC1, TOC1). PubMed:28877763

Appears in Networks:

p(HGNC:MAPT, pmod(Ph, Tyr, 18)) positiveCorrelation act(p(HGNC:SYK)) View Subject | View Object

We found an increase in Syk activation in DNs surrounding A β deposits as well as in neurons displaying an accumu- lation of phosphorylated Tau at Y18 and elevated levels of MC1 pathogenic tau conformers in AD brain sections whereas only weak immunoreactivity for pSyk was ob- served in brain sections from a non-demented control (Figs. 15, 16 and 17). PubMed:28877763

Appears in Networks:
Annotations
MeSH
Neurites
MeSH
Brain
MeSH
Alzheimer Disease

Out-Edges 46

p(HGNC:SYK) hasVariant p(HGNC:SYK, pmod(Ph)) View Subject | View Object

Appears in Networks:

p(HGNC:SYK) partOf a(HBP:pretangles) View Subject | View Object

Appears in Networks:

p(HGNC:SYK) partOf a(HBP:"GVD bodies") View Subject | View Object

Appears in Networks:

act(p(HGNC:SYK)) negativeCorrelation p(HGNC:GSK3B, pmod(Ph, Ser, 9)) View Subject | View Object

We observed that pharmacological inhibition of Syk with BAY61-3606 stimulates Ser-9 phosphorylation of GSK3β in SH-SY5Y cells (Fig. 9, A and B) suggesting that blocking Syk activity results in GSK3β inhibition. PubMed:25331948

Appears in Networks:

act(p(HGNC:SYK)) positiveCorrelation act(p(HGNC:GSK3B), ma(kin)) View Subject | View Object

We observed that pharmacological inhibition of Syk with BAY61-3606 stimulates Ser-9 phosphorylation of GSK3β in SH-SY5Y cells (Fig. 9, A and B) suggesting that blocking Syk activity results in GSK3β inhibition. PubMed:25331948

Appears in Networks:

act(p(HGNC:SYK)) increases complex(p(HGNC:CASP8), p(HGNC:MALT1)) View Subject | View Object

For example, following sensing of fungal components by the PRR dectin 1 that is expressed on human dendritic cells, signalling via the kinase SYK leads to the formation of a complex that is composed of caspase 8 and mucosa-associated lymphoid tissue lymphoma translocation protein 1 (MALT1); this complex binds to ASC, which possibly recruits cleavage substrates53. The MALT1-ASC-caspase 8 complex directly mediates IL-1β maturation53. PubMed:23702978

Appears in Networks:
Annotations
Confidence
High
NeuroMMSigDB
Caspase subgraph
NeuroMMSigDB
Interleukin signaling subgraph

act(p(HGNC:SYK)) regulates act(complex(GO:"NF-kappaB complex")) View Subject | View Object

Tyrosine kinases, including Syk and Bruton’s tyrosine kinase (BTK), are activated following PMA treatment (49, 50), act upstream of RAS/RAF (51, 52), and mediate the activation of the NFkB pathway (53). PubMed:25331948

Appears in Networks:

p(HGNC:SYK) increases act(complex(GO:"NF-kappaB complex")) View Subject | View Object

In addition, we verified that pharmacological inhibition of Syk with BAY61-3606 resulted in a blockade of NFkB activation and that genetic down-regulation of SYK using shRNA also prevented NFkB activation (data not shown) thus highlighting Syk as a key player of NFkB activation. PubMed:25331948

Appears in Networks:

p(HGNC:SYK) regulates act(complex(GO:"NF-kappaB complex")) View Subject | View Object

The magnitude of the NFkB inhibition following (-)-nilvadipine treatment was also reduced in clones of HEK293 NFkB luciferase reporter cells in which Syk expression had been silenced (data not shown) further suggesting that Syk is required to mediate the inhibition of NFkB activity induced by (-)-nilvadipine. PubMed:25331948

Appears in Networks:

p(HGNC:SYK) increases a(CHEBI:"amyloid-beta") View Subject | View Object

We found that Syk inhibition with the selective Syk inhibitor BAY61-3606 suppresses Aβ production in 7W CHO cells overexpressing APP (Fig. 6A). PubMed:25331948

Appears in Networks:

act(p(HGNC:SYK)) increases a(CHEBI:"amyloid-beta") View Subject | View Object

Interestingly, Aβ production in 7W CHO cells transfected with SYK shRNA compared with 7W CHO cells (Fig. 6C) was significantly reduced, further demonstrating the involvement of Syk in the regulation of Aβ production. PubMed:25331948

Appears in Networks:

act(p(HGNC:SYK)) decreases tloc(a(CHEBI:"amyloid-beta"), fromLoc(GO:intracellular), toLoc(MESH:Plasma)) View Subject | View Object

We show that the selective Syk inhibitor BAY61-3606 stimulates the transport of Aβ across the BBB in vitro mimicking the biological activity of (-)-nilvadipine in this model (Fig. 7A). PubMed:25331948

Appears in Networks:
Annotations
MeSH
Blood-Brain Barrier

act(p(HGNC:SYK)) increases sec(p(HBP:"sAPP-beta")) View Subject | View Object

We found that, like (-)-nilvadipine, Syk inhibition with the selective Syk inhibitor BAY61-3606 resulted in decreased sAPPβ secretion, BACE-1 mRNA, and BACE-1 protein expression (data not shown). PubMed:25331948

Appears in Networks:

act(p(HGNC:SYK)) increases r(HGNC:BACE1) View Subject | View Object

We found that, like (-)-nilvadipine, Syk inhibition with the selective Syk inhibitor BAY61-3606 resulted in decreased sAPPβ secretion, BACE-1 mRNA, and BACE-1 protein expression (data not shown). PubMed:25331948

Appears in Networks:

act(p(HGNC:SYK)) increases p(HGNC:BACE1) View Subject | View Object

We found that, like (-)-nilvadipine, Syk inhibition with the selective Syk inhibitor BAY61-3606 resulted in decreased sAPPβ secretion, BACE-1 mRNA, and BACE-1 protein expression (data not shown). PubMed:25331948

Appears in Networks:

act(p(HGNC:SYK)) increases p(HGNC:RAF1, pmod(Ph)) View Subject | View Object

As expected, RAF phosphorylation induced by PMA as well as basal RAF phosphorylation were reduced in 7W CHO cells transfected with SYK shRNA confirming a reduction in Syk activity (Fig. 6B). PubMed:25331948

Appears in Networks:

p(HGNC:SYK) regulates p(HGNC:MAPT, pmod(Ph, Tyr, 18)) View Subject | View Object

Syk has been shown to mediate the phosphorylation of Tau at Tyr-18 (56). PubMed:25331948

Appears in Networks:

act(p(HGNC:SYK)) increases act(p(HGNC:GSK3B)) View Subject | View Object

We observed that pharmacological inhibition of Syk with BAY61-3606 stimulates Ser-9 phosphorylation of GSK3β in SH-SY5Y cells (Fig. 9,Aand B) suggesting that blocking Syk activity results in GSK3β inhibition. PubMed:25331948

Appears in Networks:

p(HGNC:SYK) decreases act(p(FPLX:PKA)) View Subject | View Object

PKA is a known substrate of Syk, and it has been shown that Syk inhibits PKA activity by phosphorylating Tyr-330 of the PKA catalytic subunit (60), further supporting our observation. PubMed:25331948

Appears in Networks:

p(HGNC:SYK) decreases act(p(FPLX:PKA)) View Subject | View Object

We found that Syk inhibition with BAY61-3606 induced CREB phosphorylation, although that event is inhibited in the presence of a selective PKA inhibitor (Fig. 10, A and B) further showing that Syk inhibition results in PKA activation. PubMed:25331948

Appears in Networks:

p(HGNC:SYK) increases p(FPLX:PKA, pmod(Ph, Tyr, 330)) View Subject | View Object

PKA is a known substrate of Syk, and it has been shown that Syk inhibits PKA activity by phosphorylating Tyr-330 of the PKA catalytic subunit (60), further supporting our observation. PubMed:25331948

Appears in Networks:

p(HGNC:SYK) directlyIncreases p(HGNC:MAPT, pmod(Ph, Tyr)) View Subject | View Object

The responsible kinases include 1) proline-directed protein kinases (PDPKs) targeting SP or TP motifs [e.g., GSK3b, cyclindependent kinase (CDK)-5, and MAPKs]; 2) non–proline directed protein kinases targeting KXGS-motifs [e.g., PKA, microtubule affinity-regulating kinase and synapses of the amphid defective (SADK)]; 3) protein kinases specific for tyrosines (e.g., Src, Lck, Syk, Fyn, and c-Abl kinase) (91). PubMed:29191965

Appears in Networks:

act(p(HGNC:SYK)) positiveCorrelation bp(GO:"microglial cell activation") View Subject | View Object

To investigate whether pathological Syk activation oc- curs in the brain of AD mouse models, we analyzed the brains of 116-week-old wild-type, Tg APPsw and Tg PS1/APPsw mice using high-resolution confocal micros- copy and immunofluorescence. All transgenic mice (Fig. 1b-e) exhibit an increased Iba-1 and GFAP reactiv- ity compared to wild-type littermates (Fig. 1a). Moreo- ver,wild-type some of the activated amoeboid microglia that are observed in transgenic mice are also strongly positive for pSyk (Fig. 1b-d). PubMed:28877763

Appears in Networks:
Annotations
MeSH
Brain
MeSH
Alzheimer Disease

act(p(HGNC:SYK)) positiveCorrelation a(HBP:"amyloid-beta aggregates") View Subject | View Object

In addition, we observed that pSyk immunoreactivity is upregulated near A β plaques but neither colocalizes with microglia nor astrocytes suggesting that it could be of neuronal origin. (Fig. 1e). PubMed:28877763

Appears in Networks:
Annotations
MeSH
Brain
MeSH
Alzheimer Disease

act(p(HGNC:SYK)) positiveCorrelation a(HBP:"amyloid-beta aggregates") View Subject | View Object

In conclusion, activated Syk is not only found in microglia but also in neurons near A β deposits, par- ticularly in dystrophic neurites of Tg APPsw and Tg PS1/APPsw mice supporting a possible role of Syk activation in the formation of dystrophic neurites. PubMed:28877763

Appears in Networks:
Annotations
MeSH
Neurites
MeSH
Neurons

act(p(HGNC:SYK)) positiveCorrelation a(HBP:"amyloid-beta aggregates") View Subject | View Object

We found an increase in Syk activation in DNs surrounding A β deposits as well as in neurons displaying an accumu- lation of phosphorylated Tau at Y18 and elevated levels of MC1 pathogenic tau conformers in AD brain sections whereas only weak immunoreactivity for pSyk was ob- served in brain sections from a non-demented control (Figs. 15, 16 and 17). PubMed:28877763

Appears in Networks:
Annotations
MeSH
Neurites
MeSH
Brain
MeSH
Alzheimer Disease

p(HGNC:SYK) regulates p(HGNC:BACE1) View Subject | View Object

Dystrophic neurites are characterized by an accumula- tion of BACE-1 and sAPP β [31] and our previous work [28] has shown that Syk regulates BACE-1 expression and sAPP β levels suggesting that Syk upregulation in dystrophic neurites could contribute to the accumulation of BACE-1 and sAPP β . PubMed:28877763

Appears in Networks:
Annotations
MeSH
Neurites
MeSH
Neurons

p(HGNC:SYK) regulates p(HBP:"sAPP-beta") View Subject | View Object

Dystrophic neurites are characterized by an accumula- tion of BACE-1 and sAPP β [31] and our previous work [28] has shown that Syk regulates BACE-1 expression and sAPP β levels suggesting that Syk upregulation in dystrophic neurites could contribute to the accumulation of BACE-1 and sAPP β . PubMed:28877763

Appears in Networks:
Annotations
MeSH
Neurites
MeSH
Neurons

p(HGNC:SYK) association a(HBP:"Tau aggregates") View Subject | View Object

Most importantly, pathological tau species clearly colo- calize with pSyk (Y525/526) in hippocampal neurons (Fig. 4b). PubMed:28877763

Appears in Networks:
Annotations
Cell Ontology (CL)
hippocampal neuron

p(HGNC:SYK) association a(HBP:"Tau aggregates") View Subject | View Object

We observed a colocalization between pSyk and pTau (S202) immuno- reactivities in cortical neurons. PubMed:28877763

Appears in Networks:
Annotations
Cell Ontology (CL)
cerebral cortex neuron

p(HGNC:SYK) positiveCorrelation a(HBP:"Tau aggregates") View Subject | View Object

In general, we found that neurons that exhibit a high level of pSyk immunoreactivity also demonstrate a higher level of tau pathogenic species whereas neurons that are weakly immunopositive for pSyk show less tau pathology (Figs. 9, 10, 11, 12 and 13). PubMed:28877763

Appears in Networks:
Annotations
MeSH
Neurons

act(p(HGNC:SYK)) association p(HGNC:MAPT, pmod(HBP:hyperphosphorylation)) View Subject | View Object

Abnormal Syk activation seems to fol- low tau hyperphosphorylation (S202) in the hippocampus of Tg P301S mice (Fig. 6), as well as the formation of MC1-tau pathological conformers (data not shown here but MC1 and pSyk colocalization were quantified below). PubMed:28877763

Appears in Networks:
Annotations
MeSH
Hippocampus

p(HGNC:SYK) positiveCorrelation p(HGNC:MAPT, pmod(Ph, Tyr, 18)) View Subject | View Object

We found that tau phosphorylation at Y18 is significantly increased in neurons that are also immunopositive for pSyk (Fig. 10d, p < 0.05) which is consistent with previous data showing that in vitro Syk can phosphorylates tau at Y18. PubMed:28877763

Appears in Networks:
Annotations
MeSH
Neurons

act(p(HGNC:SYK), ma(kin)) directlyIncreases p(HGNC:MAPT, pmod(Ph, Tyr, 18)) View Subject | View Object

We found that tau phosphorylation at Y18 is significantly increased in neurons that are also immunopositive for pSyk (Fig. 10d, p < 0.05) which is consistent with previous data showing that in vitro Syk can phosphorylates tau at Y18. PubMed:28877763

Appears in Networks:

act(p(HGNC:SYK)) directlyIncreases p(HGNC:MAPT, pmod(Ph, Tyr, 18)) View Subject | View Object

Altogether, these data suggest that only certain pathogenic forms of tau (MC1, Y18) promote Syk activation, whereas Syk activation appears to directly in- duce tau phosphorylation at Y18 and to indirectly regulate tau phosphorylation at multiple epitopes (S396/404, S202) as well as tau misfolding (MC1, TOC1). PubMed:28877763

Appears in Networks:

p(HGNC:SYK) increases p(HGNC:MAPT, pmod(Ph, Tyr, 18)) View Subject | View Object

Interestingly, Syk up- regulation in SH-SY5Y cells leads to a significant in- crease (1.7-fold) in phosphorylated tau at Y18 (Fig. 14c, p < 0.01) and at S396/404 (Fig. 14d, 3-fold, p < 0.0001) compared to control cells. PubMed:28877763

Appears in Networks:

act(p(HGNC:SYK)) positiveCorrelation p(HGNC:MAPT, pmod(Ph, Tyr, 18)) View Subject | View Object

We found an increase in Syk activation in DNs surrounding A β deposits as well as in neurons displaying an accumu- lation of phosphorylated Tau at Y18 and elevated levels of MC1 pathogenic tau conformers in AD brain sections whereas only weak immunoreactivity for pSyk was ob- served in brain sections from a non-demented control (Figs. 15, 16 and 17). PubMed:28877763

Appears in Networks:
Annotations
MeSH
Neurites
MeSH
Brain
MeSH
Alzheimer Disease

p(HGNC:SYK) increases act(p(HGNC:GSK3B)) View Subject | View Object

We have previously shown that Syk positively regulates GSK-3 β activity in vitro. PubMed:28877763

Appears in Networks:

act(p(HGNC:SYK)) increases p(HGNC:MAPT, pmod(Ph, Ser, 396), pmod(Ph, Ser, 404)) View Subject | View Object

Altogether, these data suggest that only certain pathogenic forms of tau (MC1, Y18) promote Syk activation, whereas Syk activation appears to directly in- duce tau phosphorylation at Y18 and to indirectly regulate tau phosphorylation at multiple epitopes (S396/404, S202) as well as tau misfolding (MC1, TOC1). PubMed:28877763

Appears in Networks:

p(HGNC:SYK) increases p(HGNC:MAPT, pmod(Ph, Ser, 396), pmod(Ph, Ser, 404)) View Subject | View Object

Interestingly, Syk up- regulation in SH-SY5Y cells leads to a significant in- crease (1.7-fold) in phosphorylated tau at Y18 (Fig. 14c, p < 0.01) and at S396/404 (Fig. 14d, 3-fold, p < 0.0001) compared to control cells. PubMed:28877763

Appears in Networks:

act(p(HGNC:SYK)) increases p(HGNC:MAPT, pmod(Ph, Ser, 202)) View Subject | View Object

Altogether, these data suggest that only certain pathogenic forms of tau (MC1, Y18) promote Syk activation, whereas Syk activation appears to directly in- duce tau phosphorylation at Y18 and to indirectly regulate tau phosphorylation at multiple epitopes (S396/404, S202) as well as tau misfolding (MC1, TOC1). PubMed:28877763

Appears in Networks:

act(p(HGNC:SYK)) increases p(HGNC:MAPT, pmod(HBP:misfolded)) View Subject | View Object

Altogether, these data suggest that only certain pathogenic forms of tau (MC1, Y18) promote Syk activation, whereas Syk activation appears to directly in- duce tau phosphorylation at Y18 and to indirectly regulate tau phosphorylation at multiple epitopes (S396/404, S202) as well as tau misfolding (MC1, TOC1). PubMed:28877763

Appears in Networks:

act(p(HGNC:SYK)) positiveCorrelation p(HGNC:MAPT, pmod(HBP:misfolded)) View Subject | View Object

We found an increase in Syk activation in DNs surrounding A β deposits as well as in neurons displaying an accumu- lation of phosphorylated Tau at Y18 and elevated levels of MC1 pathogenic tau conformers in AD brain sections whereas only weak immunoreactivity for pSyk was ob- served in brain sections from a non-demented control (Figs. 15, 16 and 17). PubMed:28877763

Appears in Networks:
Annotations
MeSH
Neurites
MeSH
Brain
MeSH
Alzheimer Disease

p(HGNC:SYK) increases p(HGNC:MAPT) View Subject | View Object

Total tau levels are also sig- nificantly increased following Syk overexpression (Fig. 14e, 4.2-fold, p < 0.0001). PubMed:28877763

Appears in Networks:

p(HGNC:SYK) causesNoChange r(HGNC:MAPT) View Subject | View Object

We analyzed the possible impact of Syk overexpression on Tau mRNA levels by quantitative RT-PCR and found that Syk overexpression does not affect Tau transcription (data not shown) sug- gesting that Syk may regulate tau degradation or tau protein translation. PubMed:28877763

Appears in Networks:

p(HGNC:SYK) directlyIncreases p(HGNC:MAPT, pmod(Ph, Tyr, 18)) View Subject | View Object

In addition, tau can be phosphorylated by tyrosine kinases such as the SRC family members LCK, SYK and FYN at Tyr18, and the ABL family members ARG and ABL1 at Tyr394 (REF. 45). PubMed:26631930

Appears in Networks:

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