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

EMBO J. 2006 Nov 15;25(22):5284-93. doi: 10.1038/sj.emboj.7601406. Epub 2006 Nov 2.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Adhesion*
  • Cell Movement*
  • Cell-Matrix Junctions
  • Cells, Cultured
  • Chlorocebus aethiops
  • Cytoskeletal Proteins / physiology*
  • Enzyme Activation
  • Extracellular Matrix / physiology
  • Extracellular Signal-Regulated MAP Kinases / metabolism*
  • Humans
  • Mice
  • Microfilament Proteins / genetics
  • Microfilament Proteins / physiology*
  • Mutation
  • Paxillin / metabolism
  • Protein Binding
  • Signal Transduction
  • Vinculin / metabolism

Substances

  • Cytoskeletal Proteins
  • Microfilament Proteins
  • Paxillin
  • ponsin
  • Vinculin
  • Extracellular Signal-Regulated MAP Kinases