GPVI-mediated activation cascade

Stable Identifier
Homo sapiens
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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
11943772 Association of Fyn and Lyn with the proline-rich domain of glycoprotein VI regulates intracellular signaling

Suzuki-Inoue, K, Moroi, M, Bori-Sanz, T, Inoue, O, Berndt, MC, Watson, SP, Tulasne, D, Andrews, RK, Jung, SM, Shen, Y

J Biol Chem 2002
16102042 GPVI and integrin alphaIIb beta3 signaling in platelets

Auger, JM, Watson, SP, Pearce, AC, McCarty, OJ

J Thromb Haemost 2005
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