Regulation of integrin-mediated cellular responses through assembly of a CAS/Crk scaffold

Biochim Biophys Acta. 2004 Jul 5;1692(2-3):63-76. doi: 10.1016/j.bbamcr.2004.03.006.

Abstract

The molecular coupling of CAS and Crk in response to integrin activation is an evolutionary conserved signaling module that controls cell proliferation, survival and migration. However, when deregulated, CAS/Crk signaling also contributes to cancer progression and developmental defects in humans. Here we highlight recent advances in our understanding of how CAS/Crk complexes assemble in cells to modulate the actin cytoskeleton, and the molecular mechanisms that regulate this process. We discuss in detail the spatiotemporal dynamics of CAS/Crk assembly and how this scaffold recruits specific effector proteins that couple integrin signaling networks to the migration machinery of cells. We also highlight the importance of CAS/Crk signaling in the dual regulation of cell migration and survival mechanisms that operate in invasive cells during development and pathological conditions associated with cancer metastasis.

Publication types

  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Animals
  • Cell Movement
  • Cell Survival
  • Crk-Associated Substrate Protein
  • Fluorescence Resonance Energy Transfer
  • Humans
  • Integrins / genetics
  • Integrins / physiology*
  • Phosphorylation
  • Protein Conformation
  • Protein Structure, Tertiary
  • Proteins / chemistry
  • Proteins / genetics
  • Proteins / metabolism*
  • Proto-Oncogene Proteins / chemistry
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins / metabolism*
  • Proto-Oncogene Proteins c-abl / metabolism
  • Proto-Oncogene Proteins c-crk
  • Retinoblastoma-Like Protein p130

Substances

  • BCAR1 protein, human
  • Crk-Associated Substrate Protein
  • Integrins
  • Proteins
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-crk
  • Retinoblastoma-Like Protein p130
  • Proto-Oncogene Proteins c-abl