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Blood, 15 December 2000, Vol. 96, No. 13, pp. 4246-4253
HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY
Fyn and Lyn phosphorylate the Fc receptor  chain downstream of
glycoprotein VI in murine platelets, and Lyn regulates a novel
feedback pathway
Lynn S. Quek,
Jean-Max Pasquet,
Ingeborg Hers,
Richard Cornall,
Graham Knight,
Michael Barnes,
Margaret L. Hibbs,
Ashley
R. Dunn,
Clifford A. Lowell, and
Steve P. Watson
From the Department of Pharmacology, University of
Oxford; the Nuffield Department of Medicine, John Radcliffe Hospital,
Headington, Oxford; the Department of Biochemistry, University of
Cambridge, Cambridge, United Kingdom; the Ludwig Institute for Cancer
Research, Melbourne Tumour Biology Branch, Royal Melbourne Hospital,
Victoria, Australia; and the Department of Laboratory Medicine,
University of California at San Francisco, San Francisco, CA.
Activation of platelets by collagen is mediated by the complex
glycoprotein VI (GPVI)/Fc receptor  (FcR 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 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  -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 PLC2
activation after the ligation of GPVI. Lyn plays an additional role in
inhibiting platelet activation through an uncharacterized inhibitory pathway.
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