Vav family proteins are required for optimal regulation of PLCγ2 by integrin αIIbβ3

Andrew C. Pearce, Owen J.T. McCarty, Simon D.J. Calaminus, Elena Vigorito, Martin Turner, Steve P. Watson

Research output: Contribution to journalArticle

38 Scopus citations

Abstract

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 PLCγ (phospholipase Cγ) isoforms by ITAM (immunoreceptor tyrosine-based activation motif) receptors, including the platelet collagen receptor GPVI (glycoprotein VI). Vav proteins are also regulated downstream of integrins, including the major platelet integrin αIIbβ3, which has recently been shown to regulate PLCγ 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 Vav 1 and Vav3. Wild-type mouse platelets undergo a limited degree of spreading on fibrinogen, characterized by the 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 αIIbβ3-mediated PLCγ2 tyrosine phosphorylation and reduced Ca2+ mobilization. In contrast, the G-protein agonist thrombin stimulates full spreading of control and Vav1/3-deficient platelets. Consistent with this, stimulation of F-actin (filamentous 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 PLCγ2 by integrin αIIbβ3, but that their requirement is by-passed upon G-protein receptor activation.

Original languageEnglish (US)
Pages (from-to)753-761
Number of pages9
JournalBiochemical Journal
Volume401
Issue number3
DOIs
StatePublished - Feb 1 2007

Keywords

  • Fibrinogen
  • Integrin αIIbβ3
  • Phospholipase Cγ2 (PLCγ2)
  • Platelet spreading
  • Signalling
  • Vav

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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    Pearce, A. C., McCarty, O. J. T., Calaminus, S. D. J., Vigorito, E., Turner, M., & Watson, S. P. (2007). Vav family proteins are required for optimal regulation of PLCγ2 by integrin αIIbβ3. Biochemical Journal, 401(3), 753-761. https://doi.org/10.1042/BJ20061508