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Vol. 17, Issue 6, 2684-2695, June 2006

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Fibronectin Rigidity Response through Fyn and p130Cas Recruitment to the Leading Edge

Department of Biological Sciences, Columbia University, New York, NY 10027

Submitted December 21, 2005; Revised March 17, 2006; Accepted March 28, 2006
Monitoring Editor: Jean Schwarzbauer

Cell motility on extracellular matrices critically depends on matrix rigidity, which affects cell adhesion and formation of focal contacts. Receptor-like protein tyrosine phosphatase alpha (RPTP) and the _v3 integrin form a rigidity-responsive complex at the leading edge. Here we show that the rigidity response through increased spreading and growth correlates with leading edge recruitment of Fyn, but not endogenous c-Src. Recruitment of Fyn requires the palmitoylation site near the N-terminus and addition of that site to c-Src enables it to support a rigidity response. In all cases, the rigidity response correlates with the recruitment of the Src family kinase to early adhesions. The stretch-activated substrate of Fyn and c-Src, p130Cas, is also required for a rigidity response and it is phosphorylated at the leading edge in a Fyn-dependent process. A possible mechanism for the fibronectin rigidity response involves force-dependent Fyn phosphorylation of p130Cas with rigidity-dependent displacement. With the greater displacement of Fyn from p130Cas on softer surfaces, there will be less phosphorylation. These studies emphasize the importance of force and nanometer-level movements in cell growth and function.

The online version of this article contains supplemental material at MBC Online (http://www.molbiolcell.org).

Address correspondence to: Michael P. Sheetz ( ms2001{at}columbia.edu)

Abbreviations used: ECM, extracellular matrix; FN, fibronectin; RPTP, receptor-like protein tyrosine phosphatase alpha; SFK, Src family kinase.

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