Collagen phagocytosis is regulated by the guanine nucleotide exchange factor Vav2

Am J Physiol Cell Physiol. 2008 Jul;295(1):C130-7. doi: 10.1152/ajpcell.00168.2008. Epub 2008 Apr 23.


Collagen phagocytosis is a crucial alpha2beta1-integrin-dependent process that mediates extracellular matrix remodeling by fibroblasts. We showed previously that after initial contact with collagen, activated Rac1 accelerates collagen phagocytosis but the Rac guanine nucleotide exchange factors (GEFs) that regulate Rac are not defined. We examined here the GEFs that regulate collagen phagocytosis in mouse fibroblasts. Collagen binding enhanced Rac1 activity (5-20 min) but not Cdc42 or RhoA activity. Analysis of collagen bead-associated proteins showed enrichment with Vav2, which correlated temporally with increased Rac1 activity. Knockdown of Vav2 prevented Rac activation, recruitment of Rac1 to collagen bead binding sites, and collagen bead binding, but knockdown of Sos-1 or beta-Pix had no effect on Rac activation or collagen binding. Vav2 was associated with the nucleotide-free Rac1 mutant (G15ARac1) after collagen binding. Collagen bead binding promoted phosphorylation of Vav2, which temporally correlated with Rac1 activation and which required Src kinase activity. Blockage of Src activity prevented collagen bead-induced Rac activation and collagen bead binding. Collectively these data indicate that Vav2 regulates the Rac1 activity associated with the binding step of collagen phagocytosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Collagen / physiology*
  • Guanine Nucleotide Exchange Factors / metabolism
  • Mice
  • NIH 3T3 Cells
  • Phagocytosis
  • Proto-Oncogene Proteins c-vav / physiology*
  • Rho Guanine Nucleotide Exchange Factors
  • SOS1 Protein / metabolism
  • cdc42 GTP-Binding Protein / metabolism
  • rac1 GTP-Binding Protein / metabolism
  • rho GTP-Binding Proteins / metabolism
  • src-Family Kinases / metabolism


  • Guanine Nucleotide Exchange Factors
  • Proto-Oncogene Proteins c-vav
  • Rho Guanine Nucleotide Exchange Factors
  • SOS1 Protein
  • Vav2 protein, mouse
  • Collagen
  • src-Family Kinases
  • cdc42 GTP-Binding Protein
  • rac1 GTP-Binding Protein
  • rho GTP-Binding Proteins