A role for Ras in v-Crk transformation.
The v-crk oncogene, identified as the transforming gene of the CT10 avian sarcoma virus, encodes an adaptor protein capable of transforming chicken embryo fibroblasts (CEFs). Because the Src homology 3 domain of v-Crk is capable of binding the Ras family guanine nucleotide exchange factors Sos and C3G, the contribution of cellular Ras to signaling by v-Crk was evaluated. NIH-3T3 cell lines stably expressing the v-crk oncogene exhibited a transformed phenotype similar to that of CT10-infected CEFs. Treatment of these cells with a farnesylation inhibitor, as well as coexpression of dominant negative Ras, caused morphological reversion of the v-Crk NIH-3T3 cells. Dominant negative Ras expression also inhibited colony formation in soft agar without affecting tyrosine phosphorylation of cellular proteins. Although elevation of basal Erk activity could be demonstrated in v-Crk-transformed CEFs, no significant elevation of basal Erk activity was observed in the v-Crk-transformed NIH-3T3 cells. This suggests that v-Crk requires Ras function for transformation of NIH-3T3 cells and may utilize a Ras effector other than Erk to maintain the transformed phenotype.
Greulich
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Laboratory of Molecular Oncology, Rockefeller University, New York, New York 10021, USA.
Hanafusa
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H
D016475:3T3 Cells; D000818:Animals; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000032:analysis; D002471:Cell Transformation, Neoplastic; D002642:Chick Embryo; D004789:Enzyme Activation; D005347:Fibroblasts; D005799:Genes, Dominant; D051379:Mice; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D009842:Oligopeptides / Q000494:pharmacology; D050736:Oncogene Protein v-crk; D009857:Oncogenes / Q000235:genetics / Q000502:physiology*; D010766:Phosphorylation; D017368:Protein Prenylation; D015682:Retroviridae Proteins, Oncogenic / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction; D014162:Transfection; D014443:Tyrosine / Q000378:metabolism; D018631:ras Proteins / Q000235:genetics / Q000502:physiology*; D018909:src Homology Domains
D009842:Oligopeptides; D050736:Oncogene Protein v-crk; D015682:Retroviridae Proteins, Oncogenic; C088459:B 581; D014443:Tyrosine; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D018631:ras Proteins