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Activation of platelets by collagen is mediated by the complex glycoprotein VI (GPVI)/Fc receptor gamma (FcR gamma chain). In the current study, the role of 2 Src family kinases, Fyn and Lyn, in GPVI signaling has been examined using murine platelets deficient in one or both kinases. In the fyn(-/-) platelets, tyrosine phosphorylation of FcR gamma chain, phopholipase C (PLC) activity, aggregation, and secretion are reduced, though the time of onset 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 responses, followed by recovery of phosphorylation and potentiation of aggregation and alpha-granule secretion. Tyrosine phosphorylation and aggregation in response to stimulation by collagen-related peptide is further attenuated and delayed in fyn(-/-)lyn(-/-) double-mutant platelets, and potentiation is not seen. This study provides the first genetic evidence that Fyn and Lyn mediate FcR immune receptor tyrosine-based activation motif phosphorylation and PLC gamma 2 activation after the ligation of GPVI. Lyn plays an additional role in inhibiting platelet activation through an uncharacterized inhibitory pathway. (Blood. 2000;96:4246-4253)

Type

Journal article

Journal

Blood

Publication Date

15/12/2000

Volume

96

Pages

4246 - 4253

Keywords

Animals, Blood Platelets, Carrier Proteins, Collagen, Feedback, Isoenzymes, Male, Mice, Mice, Knockout, Phospholipase C gamma, Phosphorylation, Platelet Activation, Platelet Membrane Glycoproteins, Protein Processing, Post-Translational, Proteins, Proto-Oncogene Proteins, Proto-Oncogene Proteins c-fyn, Receptors, IgG, Signal Transduction, Type C Phospholipases, src-Family Kinases