J. Cell Biol., Volume 140, Number 4, February 23, 1998 961-972

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

Richard L. Klemke,^* Jie Leng,^* Rachel Molander,^* Peter C. Brooks,^* Kristiina Vuori, and David A. Cheresh^*

^* Departments of Immunology and Vascular Biology, The Scripps Research Institute, La Jolla, California 92037;  The La Jolla Cancer Research Center, The Burnham Institute, La Jolla, California 92037

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.

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• Yigzaw, Y., Poppleton, H. M., Sreejayan, N., Hassid, A., Patel, T. B. (2003). Protein-tyrosine Phosphatase-1B (PTP1B) Mediates the Anti-migratory Actions of Sprouty. J. Biol. Chem. 278: 284-288 [Abstract] [Full Text]  
• Zeng, L., Si, X., Yu, W.-P., Le, H. T., Ng, K. P., Teng, R. M.H., Ryan, K., Wang, D. Z.-M., Ponniah, S., Pallen, C. J. (2003). PTP{alpha} regulates integrin-stimulated FAK autophosphorylation and cytoskeletal rearrangement in cell spreading and migration. JCB 160: 137-146 [Abstract] [Full Text]  
• Hinsby, A. M., Olsen, J. V., Bennett, K. L., Mann, M. (2003). Signaling Initiated by Overexpression of the Fibroblast Growth Factor Receptor-1 Investigated by Mass Spectrometry. Mol. Cell. Proteomics 2: 29-36 [Abstract] [Full Text]  
• Lerman, O. Z., Galiano, R. D., Armour, M., Levine, J. P., Gurtner, G. C. (2003). Cellular Dysfunction in the Diabetic Fibroblast: Impairment in Migration, Vascular Endothelial Growth Factor Production, and Response to Hypoxia. Am. J. Pathol. 162: 303-312 [Abstract] [Full Text]  
• Chan, P.-C., Liang, C.-C., Yu, K.-C., Chang, M.-C., Ho, W. L., Chen, B.-H., Chen, H.-C. (2002). Synergistic Effect of Focal Adhesion Kinase Overexpression and Hepatocyte Growth Factor Stimulation on Cell Transformation. J. Biol. Chem. 277: 50373-50379 [Abstract] [Full Text]  
• Nagashima, K.-I., Endo, A., Ogita, H., Kawana, A., Yamagishi, A., Kitabatake, A., Matsuda, M., Mochizuki, N. (2002). Adaptor Protein Crk Is Required for Ephrin-B1-induced Membrane Ruffling and Focal Complex Assembly of Human Aortic Endothelial Cells. Mol. Biol. Cell 13: 4231-4242 [Abstract] [Full Text]  
• Sastry, S. K., Lyons, P. D., Schaller, M. D., Burridge, K. (2002). PTP-PEST controls motility through regulation of Rac1. J. Cell Sci. 115: 4305-4316 [Abstract] [Full Text]  

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