Vav family proteins are required for optimal regulation of PLC{gamma}2 by integrin {alpha}IIb{beta}3

Andrew C Pearce (1) , Owen Jt Mccarty , Simon Dj Calaminus , Elena Vigorito , Martin Turner , Steve P Watson

1 Institute of Biomedical Research

Vav proteins belong to the family of guanine nucleotide exchange factors for the Rho/Rac family of small G proteins. In addition, they serve as important adapter proteins for the activation of PLC{gamma} isoforms by ITAM receptors, including the platelet collagen receptor GPVI. Vav proteins are also regulated downstream of integrins, including the major platelet integrin {alpha}IIb{beta}3, which has recently been shown to regulate PLC{gamma}2. In the present study we have investigated the role of Vav family proteins in filopodia and lamellipodia formation on fibrinogen using platelets deficient in Vav1 and Vav3. Wild type mouse platelets undergo a limited degree of spreading on fibrinogen, characterised by formation of numerous filopodia and limited lamellipodia structures. Platelets deficient in Vav1 and Vav3 exhibit reduced filopodia and lamellipodia formation during spreading on fibrinogen. This is accompanied by reduced {alpha}IIb{beta}3-mediated PLC{gamma}2 phosphorylation and reduced Ca 2+} mobilisation. In contrast, the G protein agonist thrombin stimulates full spreading of control and Vav1/3-deficient platelets. Consistent with this, stimulation of F-actin formation and Rac activation by thrombin is not altered in Vav deficient cells. These results demonstrate that Vav1 and Vav3 are required for optimal spreading and regulation of PLC{gamma}2 by integrin {alpha}IIb{beta}3, but that their requirement is by-passed upon G protein receptor activation

Mots clés: Life Sciences

Andrew C Pearce, Owen Jt Mccarty, Simon Dj Calaminus, Elena Vigorito, Martin Turner, et al.. Vav family proteins are required for optimal regulation of PLC{gamma}2 by integrin {alpha}IIb{beta}3. Biochemical Journal, 2006, 401 (3), pp.753-761. ⟨10.1042/BJ20061508⟩. ⟨hal-00478679⟩