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

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

Research output: Contribution to journalArticle

33 Citations (Scopus)

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
Externally publishedYes

Fingerprint

Cell-Matrix Junctions
Vinculin
Cytoskeletal Proteins
Paxillin
Extracellular Matrix
Adhesion
Chemical activation
Cell Movement
Plakins
Focal Adhesions
src Homology Domains
MAP Kinase Signaling System
Cell Adhesion
Small Interfering RNA
Actins
Molecules
Mitogen-Activated Protein Kinase Kinases
Proteins
Agglomeration

Keywords

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

ASJC Scopus subject areas

  • Genetics
  • Cell Biology

Cite this

CAP interacts with cytoskeletal proteins and regulates adhesion-mediated ERK activation and motility. / Zhang, Mei; Liu, Jun D; Cheng, Alan; DeYoung, Stephanie M.; Chen, Xiaowei; Dold, Lisa H.; Saltiel, Alan R.

In: EMBO Journal, Vol. 25, No. 22, 15.11.2006, p. 5284-5293.

Research output: Contribution to journalArticle

Zhang, M, Liu, JD, Cheng, A, DeYoung, SM, Chen, X, Dold, LH & Saltiel, AR 2006, 'CAP interacts with cytoskeletal proteins and regulates adhesion-mediated ERK activation and motility', EMBO Journal, vol. 25, no. 22, pp. 5284-5293. https://doi.org/10.1038/sj.emboj.7601406
Zhang, Mei ; Liu, Jun D ; Cheng, Alan ; DeYoung, Stephanie M. ; Chen, Xiaowei ; Dold, Lisa H. ; Saltiel, Alan R. / CAP interacts with cytoskeletal proteins and regulates adhesion-mediated ERK activation and motility. In: EMBO Journal. 2006 ; Vol. 25, No. 22. pp. 5284-5293.
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