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586998 
Journal Article 
Involvement of Src kinases and PLC[gamma]2 in clot retraction 
Suzuki-Inoue, K; Hughes, CE; Inoue, O; Kaneko, M; Cuyun-Lira, O; Takafuta, T; Watson, SP; Ozaki, Y 
2007 
1 
Thrombosis Research
ISSN: 0049-3848 
120 
2 
251-258 
English 
17055557 
WOS:000247198700014 
The integrin [alpha]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 role for Src kinase-dependent activation of PLC[gamma]2 and MLC phosphorylation in mediating clot retraction downstream of integrin [alpha]IIb[beta]3. 
Blood platelets; Clot retraction; Integrin [alpha]IIb[beta]3; PLC[gamma]2; Src kinases; Outside-in signal