Src-dependent association of Cas and p85 phosphatidylinositol 3'-kinase in v-crk-transformed cells.
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.
Riggins
Rebecca B
RB
Department of Microbiology and Cancer Center, University of Virginia Health System, Charlottesville, VA 22908, USA.
DeBerry
Regina M
RM
Toosarvandani
Maziar D
MD
Bouton
Amy H
AH
D033942:Adaptor Proteins, Vesicular Transport / Q000378:metabolism*; D000818:Animals; D019556:COS Cells; D002461:Cell Line, Transformed; D002471:Cell Transformation, Neoplastic; D050719:Crk-Associated Substrate Protein; D006801:Humans; D046911:Macromolecular Substances; D050736:Oncogene Protein v-crk; D019869:Phosphatidylinositol 3-Kinases / Q000737:chemistry / Q000378:metabolism*; D010750:Phosphoproteins / Q000378:metabolism*; D011485:Protein Binding; D021122:Protein Subunits / Q000378:metabolism; D011506:Proteins; D051381:Rats; D050717:Retinoblastoma-Like Protein p130; D015682:Retroviridae Proteins, Oncogenic / Q000378:metabolism*; D014162:Transfection; D019061:src-Family Kinases / Q000378:metabolism*
D033942:Adaptor Proteins, Vesicular Transport; C493841:BCAR1 protein, human; C493843:Bcar1 protein, rat; D050719:Crk-Associated Substrate Protein; D046911:Macromolecular Substances; D050736:Oncogene Protein v-crk; D010750:Phosphoproteins; D021122:Protein Subunits; D011506:Proteins; D050717:Retinoblastoma-Like Protein p130; D015682:Retroviridae Proteins, Oncogenic; D019869:Phosphatidylinositol 3-Kinases; D019061:src-Family Kinases