Fibronectin rigidity response through Fyn and p130Cas recruitment to the leading edge

Ana Kostic, Michael Sheetz

Research output: Contribution to journalArticle

92 Citations (Scopus)

Abstract

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 (RPTPα) and the αvβ3 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.

Original languageEnglish (US)
Pages (from-to)2684-2695
Number of pages12
JournalMolecular Biology of the Cell
Volume17
Issue number6
DOIs
StatePublished - Jun 1 2006
Externally publishedYes

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Fibronectins
Cell Movement
Class 4 Receptor-Like Protein Tyrosine Phosphatases
Receptor-Like Protein Tyrosine Phosphatases
Phosphorylation
Lipoylation
Integrin alpha Chains
Focal Adhesions
src-Family Kinases
Growth
Cell Adhesion
Extracellular Matrix

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cell Biology

Cite this

Fibronectin rigidity response through Fyn and p130Cas recruitment to the leading edge. / Kostic, Ana; Sheetz, Michael.

In: Molecular Biology of the Cell, Vol. 17, No. 6, 01.06.2006, p. 2684-2695.

Research output: Contribution to journalArticle

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AB - 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 (RPTPα) and the αvβ3 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.

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