Integrin α2β1 induces phosphorylation-dependent and phosphorylation-independent activation of phospholipase Cγ2 in platelets: Role of Src kinase and Rac GTPase

G. F. Guidetti, B. Bernardi, A. Consonni, P. Rizzo, C. Gruppi, C. Balduini, Mauro Torti

Research output: Contribution to journalArticle


Background: Platelet adhesion promoted by integrin α2 β1 induces integrin αIIb β3 activation through the phospholipase.C (PLC)-dependent stimulation of the small GTPase Rap1b. Objective: To analyze the mechanism of PLC activation downstream of α2β1 that is required for regulation of Rap1b and αIIbβ3. Methods: Human and murine platelets were allowed to adhere to immobilized type I monomeric collagen through α2 β1. Tyrosine phosphorylation of PLCγ2, PLC activation, accumulation of GTP-bound Rap1b and fibrinogen binding were measured and compared. Results: Integrin α2β1 recruitment induced an evident PLC activation that was concomitant with robust tyrosine phosphorylation of PLCγ2, and was suppressed in platelets from PLCγ2-knockout mice. Moreover, PLCγ2-/- platelets were unable to accumulate active Rap1b and to activate αIIbβ3 upon adhesion through α2β1. Inhibition of Src kinases completely prevented tyrosine phosphorylation of PLCγ2 in adherent platelets, but did not affect its activation, and both Rap1b and αIIbβ3 stimulation occurred normally. Importantly, αIIbβ3-induced phosphorylation and activation of PLCγ2, as well as accumulation of active Rap1b, were totally suppressed by Src inhibition. Integrin α2β1 recruitment triggered the Src kinase-independent activation of the small GTPase Rac1, and activation of Rac1 was not required for PLCγ2 phosphorylation. However, when phosphorylation of PLCγ2 was blocked by the Src kinase inhibitor PP2, prevention of Rac1 activation significantly reduced PLCγ2 activation, GTP-Rap1b accumulation, and αIIbβ3 stimulation. Conclusions: Src kinases and the Rac GTPases mediate independent pathways for PLCγ2 activation downstream of α2 β1.

Original languageEnglish
Pages (from-to)1200-1206
Number of pages7
JournalJournal of Thrombosis and Haemostasis
Issue number7
Publication statusPublished - 2009



  • Integrins
  • Phospholipase C
  • Platelets
  • Rac
  • Rap1b
  • Src kinases

ASJC Scopus subject areas

  • Hematology
  • Medicine(all)

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