CAS/Crk Coupling Serves as a "Molecular Switch" for Induction of Cell Migration

• Published in: The Journal of cell biology 1998-02, Vol.140 (4), p.961-972
• Main Authors: Klemke, Richard L., Leng, Jie, Molander, Rachel, Brooks, Peter C., Vuori, Kristiina, Cheresh, David A.
• Format: Article
• Language: English
• Subjects: Animals; Antibodies; Cell adhesion; Cell lines; Cell Membrane - chemistry; Cell Membrane - metabolism; Cell motility; Cell Movement - drug effects; Cell Movement - physiology; Cells; Cellular biology; Cellular immunity; Collagens; COS Cells; Crk-Associated Substrate Protein; Extracellular Matrix - physiology; Gene Expression - genetics; Gene Expression - physiology; GTP-Binding Proteins - chemistry; GTP-Binding Proteins - metabolism; Humans; Hypoglycemic Agents - pharmacology; Insulin - pharmacology; Membrane Proteins - analysis; Molecules; 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; rac GTP-Binding Proteins; ras Proteins - chemistry; ras Proteins - metabolism; Retinoblastoma-Like Protein p130; src Homology Domains; Tumor Cells, Cultured; Tyrosine - metabolism
• ISSN: 0021-9525; 1540-8140
• DOI: 10.1083/jcb.140.4.961

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.