Loading...
Please wait, while we are loading the content...
Integrin α2β1 mediates outside-in regulation of platelet spreading on collagen through activation of Src kinases and PLCγ2
| Content Provider | Scilit |
|---|---|
| Author | Inoue, Osamu Suzuki-Inoue, Katsue Dean, William L. Frampton, Jon Watson, Steve |
| Copyright Year | 2003 |
| Description | 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 α2β1 and activation through the glycoprotein VI (GPVI)–Fc receptor (FcR) γ-chain complex. The present study extends this model by demonstrating that engagement of α2β1 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 γ-chain complex. The same events do not occur in platelet suspensions. α2β1 activation of adherent platelets stimulates tyrosine phosphorylation of many of the proteins in the GPVI–FcR γ-chain cascade, including Src, Syk, SLP-76, and PLCγ2 as well as plasma membrane calcium ATPase and focal adhesion kinase. α2β1-mediated spreading is dramatically inhibited in the presence of the Src kinase inhibitor PP2 and in PLCγ2-deficient platelets. Spreading is abolished by chelation of intracellular Ca2+. Demonstration that adhesion of platelets to collagen via α2β1 generates intracellular signals provides a new insight into the mechanisms that control thrombus formation and may explain the unstable nature of β1-deficient thrombi and why loss of the GPVI–FcR γ-chain complex has a relatively minor effect on bleeding. |
| Related Links | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2173361/pdf http://jcb.rupress.org/content/160/5/769.full.pdf |
| Ending Page | 780 |
| Page Count | 12 |
| Starting Page | 769 |
| DOI | 10.1083/jcb.200208043 |
| Journal | Journal of Cell Biology |
| Issue Number | 5 |
| Volume Number | 160 |
| Language | English |
| Publisher | Rockefeller University Press |
| Publisher Date | 2003-03-03 |
| Access Restriction | Open |
| Subject Keyword | Hematology Research and Experimental Medicine Integrin Α2β1; Blood Platelets; Cell Spreading; Plcγ2; Fak Journal: Journal of Cell Biology (Vol- 160, Issue- 5) |
| Content Type | Text |
