Journal
JOURNAL OF CELL BIOLOGY
Volume 160, Issue 5, Pages 769-780Publisher
ROCKEFELLER UNIV PRESS
DOI: 10.1083/jcb.200208043
Keywords
integrin alpha(2)beta(1); blood platelets; cell spreading; PLC gamma 2; FAK
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Collagen plays a critical role in hemostasis by promoting adhesion and activation of platelets at sites of vessel injury. In the present model of platelet-collagen interaction, adhesion is mediated via the inside-out regulation of integrin alpha(2)beta(1) and activation through the glycoprotein VI (GPVI)-Fc receptor (FcR) gamma-chain complex. The present study extends this model by demonstrating that engagement Of alpha(2)beta(1) by an integrin-specific sequence from within collagen or by collagen itself generates tyrosine kinase-based intracellular signals that lead to formation of filopodia and lamellipodia in the absence of the GPVI-FcR gamma-chain complex. The same events do not occur in platelet suspensions. alpha(2)beta(1) activation of adherent platelets stimulates tyrosine phosphorylation of many of the proteins in the GPVI-FcR gamma-chain cascade, including Src, Syk, SLP-76, and PLCgamma2 as well as plasma membrane calcium ATPase and focal adhesion kinase. alpha(2)beta(1)-mediated spreading is dramatically inhibited in the presence of the Src kinase inhibitor PP2 and in PLCgamma2-deficient platelets. Spreading is abolished by chelation of intracellular Ca2+. Demonstration that adhesion of platelets to collagen via alpha(2)beta(1) generates intracellular signals provides a new insight into the mechanisms that control thrombus formation and may explain the unstable nature of beta(1)-deficient thrombi and why loss of the GPVI-FcR gamma-chain complex has a relatively minor effect on bleeding.
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