Reactome | GPVI-mediated activation cascade

GPVI-mediated activation cascade

Stable Identifier

R-HSA-114604

DOI

10.3180/R-HSA-114604.2

Type

Pathway

Species

Homo sapiens

ReviewStatus

5/5

Locations in the PathwayBrowser

Expand all

General

SBML | | PDF

SVG | | PPTX | SBGN

Click the image above or here to open this pathway in the Pathway Browser

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.

Literature References

PubMed ID	Title	Journal	Year
16102042	GPVI and integrin alphaIIb beta3 signaling in platelets Watson, SP, Auger, JM, McCarty, OJ, Pearce, AC	J Thromb Haemost	2005
11943772	Association of Fyn and Lyn with the proline-rich domain of glycoprotein VI regulates intracellular signaling Suzuki-Inoue, K, Tulasne, D, Shen, Y, Bori-Sanz, T, Inoue, O, Jung, SM, Moroi, M, Andrews, RK, Berndt, MC, Watson, SP	J Biol Chem	2002