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

Dan P. Felsenfeld, Pamela L. Schwartzberg, Ana Venegas, Richard Tse, Michael Sheetz

Research output: Contribution to journalArticle

226 Citations (Scopus)

Abstract

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 ocv but not with β1integrins. 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.

Original languageEnglish (US)
Pages (from-to)200-206
Number of pages7
JournalNature Cell Biology
Volume1
Issue number4
DOIs
StatePublished - Jan 1 1999
Externally publishedYes

Fingerprint

src-Family Kinases
Cytoskeleton
Integrins
Cell Movement
Extracellular Matrix
Vitronectin Receptors
Integrin alphaVbeta3
Integrin alpha5beta1
Vitronectin
Focal Adhesions
Traction
Fibroblasts

ASJC Scopus subject areas

  • Cell Biology

Cite this

Selective regulation of integrin-cytoskeleton interactions by the tyrosine kinase Src. / Felsenfeld, Dan P.; Schwartzberg, Pamela L.; Venegas, Ana; Tse, Richard; Sheetz, Michael.

In: Nature Cell Biology, Vol. 1, No. 4, 01.01.1999, p. 200-206.

Research output: Contribution to journalArticle

Felsenfeld, Dan P. ; Schwartzberg, Pamela L. ; Venegas, Ana ; Tse, Richard ; Sheetz, Michael. / Selective regulation of integrin-cytoskeleton interactions by the tyrosine kinase Src. In: Nature Cell Biology. 1999 ; Vol. 1, No. 4. pp. 200-206.
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