Glycoprotein VI (GPVI) (GPVI)

Glycoprotein VI (GPVI) is a 62-65 kDa transmembrane receptor expressed exclusively on platelets and megakaryocytes, where it serves as the primary signaling receptor for collagen and fibrin [1, 2]. Upon ligand binding, GPVI initiates a signaling cascade through its associated Fc receptor gamma-chain (FcRγ), which contains immunoreceptor tyrosine-based activation motifs (ITAMs) that recruit and activate tyrosine kinases like Syk and PLCγ2 [2, 4]. This signaling pathway is regulated by the protein tyrosine phosphatase SHP-2 (Src homology region 2 domain-containing phosphatase-2), which acts as a negative regulator of GPVI-mediated activation by dephosphorylating key signaling components [7]. The GPVI/SHP-2 signaling axis is a critical therapeutic target; GPVI inhibitors like glenzocimab and revacept are being developed to prevent arterial thrombosis with minimal bleeding risk, while SHP-2 inhibitors are explored to modulate platelet responsiveness in conditions like Noonan syndrome [7, 9, 11]. Dysregulation of this axis is linked to myocardial infarction, ischemic stroke, and various thrombo-inflammatory diseases [1, 8].

Other names

GP6Platelet glycoprotein VICollagen receptorFibrin receptorGPVI/SHP-2 signaling axis

GPVI antagonism, inhibition of collagen and fibrin binding to platelets, and allosteric inhibition of SHP-2 to modulate downstream signaling pathways.