Journal
THROMBOSIS RESEARCH
Volume 120, Issue 2, Pages 251-258Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.thromres.2006.09.003
Keywords
blood platelets; clot retraction; integrin alpha(IIb)beta(3); PLC gamma 2; Src kinases; outside-in signal
Categories
Funding
- British Heart Foundation [CH/03/003/15571, PG/02/137/14627] Funding Source: Medline
- Wellcome Trust [073107] Funding Source: Medline
Ask authors/readers for more resources
The integrin U-IIb beta(3) plays a critical role in mediating clot retraction by platelets which is important in vivo in consolidating thrombus formation. Actin-myosin interaction is essential for clot retraction. In the present study, we demonstrate that the structurally distinct Src kinase inhibitors, PP2 and PD173952, significantly reduced the rate of clot retraction, but did not prevent it reaching completion. This effect was accompanied by abolition Of alpha(IIb)beta(3)-dependent protein tyrosine phosphorylation, including PLC-gamma 2. A role for PLC-gamma 2 in mediating clot retraction was demonstrated using PLC-gamma 2-deficient murine platelets. Furthermore, platelet adhesion to fibrinogen leads to MLC phosphorylation through a pathway that is inhibited by PP2 and by the PLC inhibitor, U73122. These results demonstrate a partial rote for Src kinase-dependent activation of PLC-gamma 2 and MLC phosphorylation in mediating clot retraction downstream of integrin alpha(IIb)beta(3). (C) 2006 Elsevier Ltd. All rights reserved.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available