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Cancer Genes and Genomics

Src-Dependent Association of Cas and p85 Phosphatidylinositol 3'-Kinase in v-crk-Transformed Cells¹

¹ Department of Microbiology and Cancer Center, University of Virginia Health System, Charlottesville, VA and
² United States Patent and Trademark Office, Arlington, VA

Requests for reprints: Amy H. Bouton, Department of Microbiology and Cancer Center, University of Virginia Health System, PO Box 800734, Charlottesville, VA 22908. Phone: (434) 924-2513; Fax: (434) 982-1071. E-mail: ahb8y{at}virginia.edu

Cellular changes associated with oncogenic transformation are generally caused by deregulation of signal transduction pathways. We show that, in cells transformed by the v-crk oncogene, the adapter protein Cas forms a stable complex with the p85 regulatory subunit of phosphatidylinositol 3'-kinase (PI3K) coincident with the appearance of Cas-associated PI3K activity. The interaction between Cas and p85 PI3K appears to be driven primarily by Src-dependent tyrosine phosphorylation of Cas, and mapping studies indicate that the carboxyl terminus of Cas is necessary and sufficient for binding to p85 PI3K. One of the cellular effects of v-Crk expression is to promote DNA synthesis in the presence of low serum. This effect is potentiated in Cas-null fibroblasts when wild-type Cas is expressed, but not when a Cas variant is expressed that lacks the carboxyl-terminal p85 PI3K binding region. This suggests that the association of Cas with p85 PI3K may play a role in uncoupling growth regulatory pathways through v-Crk.

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