Projects per year
Abstract
Src family kinases (SFKs) play a central role in mediating the rapid response of platelets to vascular injury. They transmit activation signals from a diverse repertoire of platelet surface receptors, including the integrin αIIbβ3, the immunoreceptor tyrosine-based activation motif-containing collagen receptor complex GPVI-FcR γ-chain, and the von Willebrand factor receptor complex GPIb-IX-V, which are essential for thrombus growth and stability. Ligand-mediated clustering of these receptors triggers an increase in SFK activity and downstream tyrosine phosphorylation of enzymes, adaptors, and cytoskeletal proteins that collectively propagate the signal and coordinate platelet activation. A growing body of evidence has established that SFKs also contribute to Gq- and Gi-coupled receptor signaling that synergizes with primary activation signals to maximally activate platelets and render them prothrombotic. Interestingly, SFKs concomitantly activate inhibitory pathways that limit platelet activation and thrombus size. In this review, we discuss past discoveries that laid the foundation for this fundamental area of platelet signal transduction, recent progress in our understanding of the distinct and overlapping functions of SFKs in platelets, and new avenues of research into mechanisms of SFK regulation. We also highlight the thrombotic and hemostatic consequences of targeting platelet SFKs.
Original language | English |
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Pages (from-to) | 2013-2024 |
Journal | Blood |
Volume | 124 |
Issue number | 13 |
DOIs | |
Publication status | Published - 25 Sept 2014 |
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Dive into the research topics of 'Src family kinases : at the forefront of platelet activation'. Together they form a unique fingerprint.Projects
- 3 Finished
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Investigation of Molecular Mechanisms Regulating Megakaryocyte and Platelet Hyperactivity and Prothrombotic Disorders in LAIR-1 and PECAM-1-Deficient Mice
Mazharian, A. (Principal Investigator), Senis, Y. (Co-Investigator) & Watson, S. (Co-Investigator)
1/04/14 → 31/03/17
Project: Research
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Regulation of Platelet Activation and Thrombosis by the G6b-B-Shp1/2 Signalling Complex
Senis, Y. (Principal Investigator)
1/01/13 → 31/12/17
Project: Research
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Regulation of Src Family Kinases in Platelets by the Kinase-Phosphatase Pair Csk-CD148
Senis, Y. (Principal Investigator) & Watson, S. (Co-Investigator)
1/01/12 → 31/12/14
Project: Research