Cookies on this website

We use cookies to ensure that we give you the best experience on our website. If you click 'Accept all cookies' we'll assume that you are happy to receive all cookies and you won't see this message again. If you click 'Reject all non-essential cookies' only necessary cookies providing core functionality such as security, network management, and accessibility will be enabled. Click 'Find out more' for information on how to change your cookie settings.

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

12/2000

Volume

96

Pages

4246 - 4253

Addresses

Department of Pharmacology, University of Oxford, United Kingdom.

Keywords

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