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

Nature Cell Biology volume 1, pages 200–206 (1999)Cite this article

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 αv but not with β1 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.

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Figure 1: Vitronectin-receptor-mediated cell spreading is selectively regulated by Src.
Figure 2: Integrin–ligand interactions are unaffected by the absence of Src.
Figure 3: Src selectively modulates integrin-mediated force generation.
Figure 4: GFP-Src distribution is substrate dependent.
Figure 5: Src-251GFP co-localizes with αv but not β1 integrins on the cell surface.

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Acknowledgements

We thank B. Capel, D. Choquet, H. Erickson, A. Felsenfeld, C. Galbraith, B. McKay and C. Nicchitta for comments on the manuscript; C. Huang, M. Khouri and J. Kuo for technical assistance; and H. Erickson, B. McKay and H. Varmus for essential discussions. This work was supported by a grant from the NIH (to M.P.S.).

Correspondence and requests for materials should be addressed to M.P.S.

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Authors and Affiliations

  1. Department of Cell Biology, Duke University Medical Center, Durham, 27710, North Carolina, USA

    Dan P. Felsenfeld, Richard Tse & Michael P. Sheetz

  2. Genetic Disease Research Branch, NHGRI, NIH, Bethesda, Maryland, 20892, USA

    Pamela L. Schwartzberg & Ana Venegas

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  1. Dan P. Felsenfeld
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Correspondence to Michael P. Sheetz.

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Felsenfeld, D., Schwartzberg, P., Venegas, A. et al. Selective regulation of integrin–cytoskeleton interactions by the tyrosine kinase Src. Nat Cell Biol 1, 200–206 (1999). https://doi.org/10.1038/12021

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