| First Author | Mangin P | Year | 2003 |
| Journal | FEBS Lett | Volume | 542 |
| Issue | 1-3 | Pages | 53-9 |
| PubMed ID | 12729897 | Mgi Jnum | J:118572 |
| Mgi Id | MGI:3699785 | Doi | 10.1016/s0014-5793(03)00337-5 |
| Citation | Mangin P, et al. (2003) A PLC gamma 2-independent platelet collagen aggregation requiring functional association of GPVI and integrin alpha2beta1. FEBS Lett 542(1-3):53-9 |
| abstractText | The role of the phospholipase C (PLC)gamma 2 isotype in platelet activation was evaluated by studying PLC gamma 2 -/- mice. These mice have a prolonged bleeding time but their platelets respond normally to non-collagenous agonists. PLC gamma 2-null platelets show residual aggregation response to collagen fibres (6% versus 74% for wild-type) with minimal granule secretion and no shape change. A delayed shape change is observed at later aggregation times. Specific activation by glycoprotein (GP)VI agonists (convulxin, collagen-related peptide and GPVI crosslinking) is, however, abolished. Antibodies against integrin alpha(2)beta(1) and GPVI each inhibit the residual collagen response, implying a role of alpha(2)beta(1) in platelet activation and a functional association with GPVI. These responses are also prevented by blocking integrin alpha(IIb)beta(3) and phosphoinositide 3-kinase, whereas aspirin treatment and ADP receptor blockade only inhibit shape change. These results provide evidence for a PLC gamma 2-independent collagen activation pathway requiring cooperation between GPVI and alpha(2)beta(1) leading to alpha(IIb)beta(3)-dependent aggregation and shape change by released ADP and thromboxane A(2). |
