Selective regulation of integrin--cytoskeleton interactions by the tyrosine kinase Src

Nat Cell Biol. 1999 Aug;1(4):200-6. doi: 10.1038/12021.


Cell motility on extracellular-matrix (ECM) substrates depends on the regulated generation of force against the substrate through adhesion receptors known as integrins. Here we show that integrin-mediated traction forces can be selectively modulated by the tyrosine kinase Src. In Src-deficient fibroblasts, cell spreading on the ECM component vitronectin is inhibited, while the strengthening of linkages between integrin vitronectin receptors and the force-generating cytoskeleton in response to substrate rigidity is dramatically increased. In contrast, Src deficiency has no detectable effects on fibronectin-receptor function. Finally, truncated Src (lacking the kinase domain) co-localizes to focal-adhesion sites with alpha v but not with beta 1 integrins. These data are consistent with a selective, functional interaction between Src and the vitronectin receptor that acts at the integrin-cytoskeleton interface to regulate cell spreading and migration.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antigens, CD / metabolism
  • Cell Adhesion / physiology
  • Cell Line
  • Cell Movement / physiology
  • Cytoskeleton / metabolism*
  • Fibroblasts / physiology
  • Green Fluorescent Proteins
  • Integrin alphaV
  • Integrin beta1 / metabolism
  • Integrins / metabolism*
  • Luminescent Proteins / genetics
  • Luminescent Proteins / metabolism
  • Mice
  • Mice, Knockout
  • Receptors, Fibronectin / metabolism
  • Receptors, Vitronectin / metabolism
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism
  • Vitronectin / metabolism
  • src-Family Kinases / genetics
  • src-Family Kinases / metabolism*


  • Antigens, CD
  • Integrin alphaV
  • Integrin beta1
  • Integrins
  • Luminescent Proteins
  • Receptors, Fibronectin
  • Receptors, Vitronectin
  • Recombinant Fusion Proteins
  • Vitronectin
  • Green Fluorescent Proteins
  • src-Family Kinases