CAS/Crk coupling serves as a "molecular switch" for induction of cell migration

J Cell Biol. 1998 Feb 23;140(4):961-72. doi: 10.1083/jcb.140.4.961.

Abstract

Carcinoma cells selected for their ability to migrate in vitro showed enhanced invasive properties in vivo. Associated with this induction of migration was the anchorage-dependent phosphorylation of p130CAS (Crk-associated substrate), leading to its coupling to the adaptor protein c-CrkII (Crk). In fact, expression of CAS or its adaptor protein partner Crk was sufficient to promote cell migration, and this depended on CAS tyrosine phosphorylation facilitating an SH2-mediated complex with Crk. Cytokine-stimulated cell migration was blocked by CAS lacking the Crk binding site or Crk containing a mutant SH2 domain. This migration response was characterized by CAS/Crk localization to membrane ruffles and blocked by the dominant-negative GTPase, Rac, but not Ras. Thus, CAS/Crk assembly serves as a "molecular switch" for the induction of cell migration and appears to contribute to the invasive property of tumors.

Publication types

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

MeSH terms

  • Animals
  • COS Cells
  • Cell Membrane / chemistry
  • Cell Membrane / metabolism
  • Cell Movement / drug effects
  • Cell Movement / physiology*
  • Crk-Associated Substrate Protein
  • Extracellular Matrix / physiology
  • GTP-Binding Proteins / chemistry
  • GTP-Binding Proteins / metabolism
  • Gene Expression / genetics
  • Gene Expression / physiology
  • Humans
  • Hypoglycemic Agents / pharmacology
  • Insulin / pharmacology
  • Membrane Proteins / analysis
  • Neoplasm Metastasis
  • Pancreas / cytology
  • Pancreas / pathology
  • Pancreas / physiopathology
  • Pancreatic Neoplasms / pathology
  • Phosphoproteins / drug effects
  • Phosphoproteins / genetics
  • Phosphoproteins / metabolism*
  • Phosphorylation
  • Protein Binding
  • Proteins*
  • Proto-Oncogene Proteins / drug effects
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins / metabolism*
  • Proto-Oncogene Proteins c-crk
  • Rabbits
  • Retinoblastoma-Like Protein p130
  • Tumor Cells, Cultured
  • Tyrosine / metabolism
  • rac GTP-Binding Proteins
  • ras Proteins / chemistry
  • ras Proteins / metabolism
  • src Homology Domains

Substances

  • BCAR1 protein, human
  • Crk-Associated Substrate Protein
  • Hypoglycemic Agents
  • Insulin
  • Membrane Proteins
  • Phosphoproteins
  • Proteins
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-crk
  • Retinoblastoma-Like Protein p130
  • Tyrosine
  • GTP-Binding Proteins
  • rac GTP-Binding Proteins
  • ras Proteins