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Integrin [[alpha].sub.2][[beta].sub.1] mediates outside-in regulation of platelet spreading on collagen through activation of Src kinases and PLC[gamma]2
- Source :
- The Journal of Cell Biology. March 3, 2003, Vol. 160 Issue 5, p769, 12 p.
- Publication Year :
- 2003
-
Abstract
- 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].sub.2][[beta].sub.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].sub.2][[beta].sub.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].sub.2][[beta].sub.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 PLC[gamma]2 as well as plasma membrane calcium ATPase and focal adhesion kinase. [[alpha].sub.2][[beta].sub.1]-mediated spreading is dramatically inhibited in the presence of the Src kinase inhibitor PP2 and in PLC[gamma]2-deficient platelets. Spreading is abolished by chelation of intracellular [Ca.sup.2+]. Demonstration that adhesion of platelets to collagen via [[alpha].sub.2][[beta].sub.1] generates intracellular signals provides a new insight into the mechanisms that control thrombus formation and may explain the unstable nature of [[beta].sub.1]-deficient thrombi and why loss of the GPVI-FcR [gamma]-chain complex has a relatively minor effect on bleeding.
- Subjects :
- Cytology -- Research
Collagen -- Physiological aspects
Collagen -- Genetic aspects
Hemostasis -- Physiological aspects
Hemostasis -- Genetic aspects
Cell adhesion -- Genetic aspects
Cell adhesion -- Physiological aspects
Glycoproteins -- Genetic aspects
Glycoproteins -- Physiological aspects
Tyrosine -- Physiological aspects
Tyrosine -- Genetic aspects
Biological sciences
Subjects
Details
- ISSN :
- 00219525
- Volume :
- 160
- Issue :
- 5
- Database :
- Gale General OneFile
- Journal :
- The Journal of Cell Biology
- Publication Type :
- Academic Journal
- Accession number :
- edsgcl.99746847