Fyn and Lyn phosphorylate the Fc receptor gamma chain downstream of glycoprotein VI in murine platelets, and Lyn regulates a novel feedback pathway

Activation of platelets by collagen is mediated by the complex glycoprotein VI (GPVI)/Fc receptor gamma (FcR gamma chain). In the current study, the r ole of 2 Src family kinases, Fyn and Lyn, in GPVI signaling has been examin ed using murine platelets deficient in one or both kinases. In the fyn(-/-) platelets, tyrosine phosphorylation of FcR gamma chain, phopholipase C (PL C) activity, aggregation, and secretion are reduced, though the time of ons et of response is unchanged. In the lyn(-/-) platelets, there is a delay of up to 30 seconds in the onset of tyrosine phosphorylation and functional r esponses, followed by recovery of phosphorylation and potentiation of aggre gation and alpha -granule secretion. Tyrosine phosphorylation and aggregati on in response to stimulation by collagen-related peptide is further attenu ated and delayed in fyn(-/-)lyn(-/-) double-mutant platelets, and potentiat ion is not seen. This study provides the first genetic evidence that Fyn an d Lyn mediate FcR immune receptor tyrosine-based activation motif phosphory lation and PLC gammaP activation after the ligation of GPVI. Lyn plays an a dditional role in inhibiting platelet activation through an uncharacterized inhibitory pathway. (C) 2000 by The American Society of Hematology.