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Article

  • The EMBO Journal (2006) 25, 5284 - 5293
  • doi:10.1038/sj.emboj.7601406

Published online: 2 November 2006

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

Mei Zhang1,2,a, Jun Liu1,2,ab, Alan Cheng1,2, Stephanie M DeYoung1,2, Xiaowei Chen1,2, Lisa H Dold1,2 and Alan R Saltiel1,2

  1. Department of Internal Medicine, Life Sciences Institute, University of Michigan, Ann Arbor, MI, USA
  2. Department of Physiology, Life Sciences Institute, University of Michigan, Ann Arbor, MI, USA

Correspondence to:

Alan R Saltiel, Departments of Internal Medicine and Physiology, Life Sciences Institute, University of Michigan, 210 Washtenaw Ave, 3rd Floor, Ann Arbor, MI 48109, USA. Tel.: +1 734 615 9787; Fax: +1 734 763 6492; E-mail: saltiel@lsi.umich.edu

aThese authors contributed equally to this work

bPresent address: Kentucky Pediatric Research Institute, University of Kentucky School of Medicine, Lexington, KY 40536, USA

Received 17 August 2006; Accepted 5 October 2006

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.

  • Keywords:

    • CAP,
    • cell–ECM adhesion,
    • ERK,
    • migration,
    • spreading