CAP interacts with cytoskeletal proteins and regulates adhesion-mediated ERK activation and motility

Mei Zhang, Jun Liu, Alan Cheng, Stephanie M. DeYoung, Xiaowei Chen, Lisa H. Dold, Alan R. Saltiel

Research output: Contribution to journalArticle

38 Scopus citations

Abstract

CAP/Ponsin belongs to the SoHo family of adaptor molecules that includes ArgBP2 and Vinexin. These proteins possess an N-terminal sorbin homology (SoHo) domain and three C-terminal SH3 domains that bind to diverse signaling molecules involved in a variety of cellular processes. Here, we show that CAP binds to the cytoskeletal proteins paxillin and vinculin. CAP localizes to cell-extracellular matrix (ECM) adhesion sites, and this process requires binding to vinculin. Overexpression of CAP induces the aggregation of paxillin, vinculin and actin at cell-ECM adhesion sites. Moreover, CAP inhibits adhesion-dependent processes such as cell spreading and focal adhesion turnover, whereas a CAP mutant that is unable to localize to cell-ECM adhesion sites is incapable of exerting these effects. Finally, depletion of CAP by siRNA-mediated knockdown leads to enhanced cell spreading, migration and the activation of the PAK/MEK/ERK pathway in REF52 cells. Taken together, these results indicate that CAP is a cytoskeletal adaptor protein involved in modulating adhesion-mediated signaling events that lead to cell migration.

Original languageEnglish (US)
Pages (from-to)5284-5293
Number of pages10
JournalEMBO Journal
Volume25
Issue number22
DOIs
StatePublished - Nov 15 2006

Keywords

  • CAP
  • Cell-ECM adhesion
  • ERK
  • Migration
  • Spreading

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

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