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PMID: 9472046 Published · ppublish English Journal Article 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.

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

The Journal of cell biology ·Vol. 140 ·No. 4 ·1998-02-23 ·Pages 961-72

Klemke RL, Leng J, Molander R, Brooks PC, Vuori K, Cheresh DA

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.

MeSH Terms
Animals COS Cells Cell Membrane/chemistry,metabolism Cell Movement/drug effects,physiology Crk-Associated Substrate Protein Extracellular Matrix/physiology GTP-Binding Proteins/chemistry,metabolism Gene Expression/genetics,physiology Humans Hypoglycemic Agents/pharmacology Insulin/pharmacology Membrane Proteins/analysis Neoplasm Metastasis Pancreas/cytology,pathology,physiopathology Pancreatic Neoplasms/pathology Phosphoproteins/drug effects,genetics,metabolism Phosphorylation Protein Binding Proteins Proto-Oncogene Proteins/drug effects,genetics,metabolism Proto-Oncogene Proteins c-crk Rabbits Retinoblastoma-Like Protein p130 Tumor Cells, Cultured Tyrosine/metabolism rac GTP-Binding Proteins ras Proteins/chemistry,metabolism src Homology Domains
Chemicals
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
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Klemke R L
Department of Immunology, The Scripps Research Institute, La Jolla, California 92037, USA. klemke@scripps.edu
Leng J
Molander R
Brooks P C
Vuori K
Cheresh D A
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Article Info
Journal
The Journal of cell biology
Abbr.
J Cell Biol
ISSN
0021-9525
DOI
10.1083/jcb.140.4.961
Email
klemke@scripps.edu
Published
1998-02-23
Pages
961-72
Language
English
Region
United States
NLM ID
0375356
PMCID
PMC2141747
Subset
IM
Grants
NHLBI NIH HHS · HL-54444 · United States
NCI NIH HHS · CA-50286 · United States
NCI NIH HHS · CA-45726 · United States
External Links
PubMed source DOI: 10.1083/jcb.140.4.961 PMC Full Text View journal details
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