GPVI-mediated activation cascade (Homo sapiens)

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1, 2192516-188, 94-611208, 97252122, 238, 924320121013-15cytosolp-SYK(Y348):p-VavATPGPVI:phosphorylated Fc Epsilon R1 gamma:FYN:LYN:Collagen I:p-SYK(Y348)p-VAV3(Y173)ATPp-SLP-76:VAVVav:PIP2Vav3 Rho/Rac effectors:GDPLATPDK1:AKTPDK1:AKT:PIP3Syk/LckSYKADPVav1 Rho/Rac effectors:GDPPI3K gamma1,2-DiacylglycerolGPVI:phosphorylated Fc Epsilon R1 gamma:FYN:LYN:Collagen IGPVI:phosphorylated Fc Epsilon R1 gamma:FYN:LYN:Collagen I:SYKPIP3:PDK1:AKT:p(T410)-PKC zetaVav3 Rho/Rac effectors:GTPGTPp-LAT (Y200,Y220)PIP3:PDK1:AKT:PKC zetap-SYK(Y348):VavVav2 Rho/Rac effectors:GDPphosphorylated SLP-76ADPGDPADPADP1-Phosphatidyl-D-myo-inositol 4,5-bisphosphateATPATPATPVav familyp-VAV1(Y174)Vav2 Rho/Rac effectors:GTPp-SYK(Y348)ADPPI3K betap-VAV2(Y172)ADPSLP-761D-myo-Inositol 1,4,5-trisphosphatePhosphatidylinositol-4,5-bisphosphateATPPI3K alpha, beta, gammaPhospholipase C gamma 2Vav1 Rho/Rac effectors:GTPPhosphatidylinositol-3,4,5-trisphosphateVAVProtein kinase C, zeta typeGPVI:FceRI gamma:FYN:LYN:Collagen IVav:PIP3Phospholipase C gamma 2, phosphorylated


Description

The GPVI receptor is a complex of the GPVI protein with Fc epsilon R1 gamma (FcR). The Src family kinases Fyn and Lyn constitutively associate with the GPVI-FcR complex in platelets and initiate platelet activation through phosphorylation of the immunoreceptor tyrosine-based activation motif (ITAM) in the FcR gamma chain, leading to binding and activation of the tyrosine kinase Syk. Downstream of Syk, a series of adapter molecules and effectors lead to platelet activation.

The GPVI receptor signaling cascade is similar to that of T- and B-cell immune receptors, involving the formation of a signalosome composed of adapter and effector proteins. At the core of the T-cell receptor signalosome is the transmembrane adapter LAT and two cytosolic adapters SLP-76 and Gads. While LAT is essential for signalling to PLCgamma1 downstream of the T-cell receptor, the absence of LAT in platelets only impairs the activation of PLCgamma2, the response to collagen and GPVI receptor ligands remains sufficient to elicit a full aggregation response. In contrast, GPVI signalling is almost entirely abolished in the absence of SLP-76.

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Bibliography

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History

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CompareRevisionActionTimeUserComment
114659view16:12, 25 January 2021ReactomeTeamReactome version 75
113107view11:17, 2 November 2020ReactomeTeamReactome version 74
112341view15:26, 9 October 2020ReactomeTeamReactome version 73
101241view11:13, 1 November 2018ReactomeTeamreactome version 66
100780view20:40, 31 October 2018ReactomeTeamreactome version 65
100323view19:17, 31 October 2018ReactomeTeamreactome version 64
99868view16:00, 31 October 2018ReactomeTeamreactome version 63
99425view14:36, 31 October 2018ReactomeTeamreactome version 62 (2nd attempt)
93862view13:41, 16 August 2017ReactomeTeamreactome version 61
93427view11:23, 9 August 2017ReactomeTeamreactome version 61
87460view14:08, 22 July 2016MkutmonOntology Term : 'hemostasis pathway' added !
87459view14:08, 22 July 2016MkutmonOntology Term : 'signaling pathway' added !
86515view09:19, 11 July 2016ReactomeTeamreactome version 56
83048view09:46, 18 November 2015ReactomeTeamVersion54
81348view12:52, 21 August 2015ReactomeTeamVersion53
76817view08:04, 17 July 2014ReactomeTeamFixed remaining interactions
76521view11:45, 16 July 2014ReactomeTeamFixed remaining interactions
75854view09:50, 11 June 2014ReactomeTeamRe-fixing comment source
75554view10:34, 10 June 2014ReactomeTeamReactome 48 Update
74909view13:43, 8 May 2014AnweshaFixing comment source for displaying WikiPathways description
74553view08:35, 30 April 2014ReactomeTeamReactome46
42049view21:53, 4 March 2011MaintBotAutomatic update
39852view05:53, 21 January 2011MaintBotNew pathway

External references

DataNodes

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NameTypeDatabase referenceComment
1,2-Diacylglycerol Unknown17815 (ChEBI)
1-Phosphatidyl-D-

myo-inositol 4,5- bisphosphate

Unknown18348 (ChEBI)
1D-myo-Inositol

1,4,5-trisphosphate

Metabolite16595 (ChEBI)
ADP Metabolite16761 (ChEBI)
ATP Metabolite15422 (ChEBI)
GDP Metabolite17552 (ChEBI)
GPVI:FceRI

gamma:FYN:LYN: Collagen I

ComplexREACT_20373 (Reactome)
GPVI:phosphorylated

Fc Epsilon R1 gamma: FYN:LYN:Collagen I

ComplexREACT_19828 (Reactome)
GPVI:phosphorylated

Fc Epsilon R1 gamma: FYN:LYN:Collagen I: SYK

ComplexREACT_19516 (Reactome)
GPVI:phosphorylated

Fc Epsilon R1 gamma: FYN:LYN:Collagen I:p- SYK(Y348)

ComplexREACT_24781 (Reactome)
GTP Metabolite15996 (ChEBI)
LAT ProteinO43561 (UniProt)
PDK1:AKT ComplexREACT_20806 (Reactome)
PDK1:AKT:PIP3 ComplexREACT_13226 (Reactome)
PI3K alpha, beta,

gamma

ComplexREACT_20768 (Reactome)
PI3K beta ComplexREACT_21094 (Reactome)
PI3K gamma ComplexREACT_20417 (Reactome)
PIP3:PDK1:AKT:PKC

zeta

ComplexREACT_21150 (Reactome)
PIP3:PDK1:AKT:p

(T410)-PKC zeta

ComplexREACT_20994 (Reactome)
Phosphatidylinositol-

3,4,5-trisphosphate

Metabolite16618 (ChEBI)
Phosphatidylinositol-

4,5-bisphosphate

Metabolite18348 (ChEBI)
Phospholipase C

gamma 2

ProteinP16885 (UniProt)
Phospholipase C

gamma 2, phosphorylated

ProteinP16885 (UniProt)
Protein kinase C,

zeta type

ProteinQ05513 (UniProt)
SLP-76 ProteinQ13094 (UniProt)
SYK ProteinP43405 (UniProt)
Syk/Lck ProteinREACT_24482 (Reactome)
VAV ProteinREACT_21165 (Reactome)
Vav family ProteinREACT_21194 (Reactome)
Vav1 Rho/Rac

effectors:GDP

ComplexREACT_4113 (Reactome)
Vav1 Rho/Rac

effectors:GTP

ComplexREACT_4042 (Reactome)
Vav2 Rho/Rac

effectors:GDP

ComplexREACT_24745 (Reactome)
Vav2 Rho/Rac

effectors:GTP

ComplexREACT_24831 (Reactome)
Vav3 Rho/Rac

effectors:GDP

ComplexREACT_24607 (Reactome)
Vav3 Rho/Rac

effectors:GTP

ComplexREACT_24491 (Reactome)
Vav:PIP2 ComplexREACT_20899 (Reactome)
Vav:PIP3 ComplexREACT_20699 (Reactome)
p-LAT (Y200,Y220) ProteinO43561 (UniProt)
p-SLP-76:VAV ComplexREACT_20942 (Reactome)
p-SYK(Y348) ProteinP43405 (UniProt)
p-SYK(Y348):

Vav

ComplexREACT_24120 (Reactome)
p-SYK(Y348):p-

Vav

ComplexREACT_24454 (Reactome)
p-VAV1(Y174) ProteinP15498 (UniProt)
p-VAV2(Y172) ProteinP52735 (UniProt)
p-VAV3(Y173) ProteinQ9UKW4 (UniProt)
phosphorylated SLP-

76

ProteinQ13094 (UniProt)

Annotated Interactions

No annotated interactions

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