Vav GEFs are required for β2 integrin-dependent functions of neutrophils

M. Angelica Martinez Gakidis, Xavier Cullere, Timothy Olson, Julie L. Wilsbacher, Bin Zhang, Sheri L. Moores, Klaus Ley, Wojciech Swat, Tanya Mayadas, Joan S. Brugge

Research output: Contribution to journalArticlepeer-review

186 Scopus citations


Integrin regulation of neutrophils is essential for appropriate adhesion and transmigration into tissues. Vav proteins are Rho family guanine nucleotide exchange factors that become tyrosine phosphorylated in response to adhesion. Using Vav1/Vav3-deficient neutrophils (Vav1/3ko), we show that Vav proteins are required for multiple β2 integrin-dependent functions, including sustained adhesion, spreading, and complement-mediated phagocytosis. These defects are not attributable to a lack of initial β2 activation as Vav1/3ko neutrophils undergo chemoattractant-induced arrest on intercellular adhesion molecule-1 under flow. Accordingly, in vivo, Vav1/3ko leukocytes arrest on venular endothelium yet are unable to sustain adherence. Thus, Vav proteins are specifically required for stable adhesion. β2-induced activation of Cdc42, Rac1, and RhoA is defective in Vav1/3ko neutrophils, and phosphorylation of Pyk2, paxillin, and Akt is also significantly reduced. In contrast, Vav proteins are largely dispensable for G protein-coupled receptor-induced signaling events and chemotaxis. Thus, Vav proteins play an essential role coupling β2 to Rho GTPases and regulating multiple integrin-induced events important in leukocyte adhesion and phagocytosis.

Original languageEnglish (US)
Pages (from-to)273-282
Number of pages10
JournalJournal of Cell Biology
Issue number2
StatePublished - Jul 19 2004
Externally publishedYes


  • Cell adhesion
  • Chemotaxis
  • Integrins
  • Phagocytosis
  • Rho GTPases

ASJC Scopus subject areas

  • Cell Biology


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