N-WASP-directed actin polymerization activates Cas phosphorylation and lamellipodium spreading

Xian Zhang, Simon W. Moore, Thomas Iskratsch, Michael Sheetz

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

Tyrosine phosphorylation of the substrate domain of Cas (CasSD) correlates with increased cell migration in healthy and diseased cells. Here, we address the mechanism leading to the phosphorylation of CasSD in the context of fibronectin-induced early spreading of fibroblasts. We have previously demonstrated that mechanical stretching of CasSD exposes phosphorylation sites for Src family kinases (SFKs). Surprisingly, phosphorylation of CasSD was independent of myosin contractile activity but dependent on actin polymerization. Furthermore, we found that CasSD phosphorylation in the early stages of cell spreading required: (1) integrin anchorage and integrin-mediated activation of SFKs, (2) association of Cas with focal adhesion kinase (FAK), and (3) N-WASP-driven actin-assembly activity. These findings, and analyses of the interactions of the Cas domains, indicate that the N-terminus of Cas associates with the FAK-N-WASP complex at the protrusive edge of the cell and that the C-terminus of Cas associates with the immobilized integrin-SFK cluster. Thus, extension of the leading edge mediated by actin polymerization could stretch Cas during early cell spreading, priming it for phosphorylation.

Original languageEnglish (US)
Pages (from-to)1394-1405
Number of pages12
JournalJournal of Cell Science
Volume127
Issue number7
DOIs
StatePublished - Jan 1 2014
Externally publishedYes

Fingerprint

Pseudopodia
Polymerization
Actins
Phosphorylation
src-Family Kinases
Integrins
Focal Adhesion Protein-Tyrosine Kinases
Myosins
Fibronectins
Cell Movement
Tyrosine
Fibroblasts

Keywords

  • Actin dynamics
  • BCAR1
  • Cas
  • Crk-associatied substrate
  • FAK
  • Focal adhesion kinase
  • p130Cas
  • SFK
  • Src family kinase

ASJC Scopus subject areas

  • Cell Biology
  • Medicine(all)

Cite this

N-WASP-directed actin polymerization activates Cas phosphorylation and lamellipodium spreading. / Zhang, Xian; Moore, Simon W.; Iskratsch, Thomas; Sheetz, Michael.

In: Journal of Cell Science, Vol. 127, No. 7, 01.01.2014, p. 1394-1405.

Research output: Contribution to journalArticle

Zhang, Xian ; Moore, Simon W. ; Iskratsch, Thomas ; Sheetz, Michael. / N-WASP-directed actin polymerization activates Cas phosphorylation and lamellipodium spreading. In: Journal of Cell Science. 2014 ; Vol. 127, No. 7. pp. 1394-1405.
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