Platelet GPIb‐IX‐V‐dependent signaling

Although the signaling pathways related to GPIb‐IX‐V have not been fully elucidated, an accumulating body of evidence suggests that phospholipase C (PLC)γ2 activation, subsequent Ca++ release and oscillations constitute an essential signal transduction pathway related to GPIb‐IX‐V. Src family kinases are required for PLCγ2 activation, while FcRγ‐chain/FcγRIIA may be dispensable for PLCγ2 activation. Although PI‐3K serves to potentiate various signaling events culminating in αIIbβ3 activation, PI‐3K activity may be dispensable for Src‐PLCγ2 activation in GPIb‐IX‐V‐mediated signaling. Glycosphingolipid‐enriched microdomains (GEMs) appear to provide platforms for the signal transduction pathway related to GIb‐IX‐V, as the interaction between GPIb‐IX‐V and Src or PLCγ2 tyrosine phosphorylation occurs exclusively in GEMs.