Ras-independent transformation by v-Src.
Signaling by a variety of receptor and nonreceptor tyrosine kinases is mediated by Ras, a membrane-associated GTPase. Expression of v-Src, a transforming nonreceptor tyrosine kinase, results in Ras activation, and inhibition of Ras function in NIH 3T3 cells suppresses transformation by v-Src, indicating that in these cells Ras-dependent signaling pathways are required for v-Src to exert its biological effects. However, we show here that Ras was not activated in Rat-2 fibroblasts transformed by wild-type v-Src, or in chicken embryo fibroblasts transformed by SRX5, a v-Src mutant with a linker insertion at the major site of autophosphorylation. Expression of a dominant-negative mutant of Ras completely inhibited the ability of v-Src to activate the mitogen-activated protein kinase ERK2, which is downstream of Ras. However, dominant-negative Ras did not suppress transformation by v-Src as judged by a variety of criteria. Thus, v-Src can transform at least some cell types in the absence of Ras activation or Ras-stimulated ERK2 activity, and in these cells activation of Ras-independent signaling pathways must therefore be sufficient for transformation.
Aftab
D T
DT
Department of Molecular and Cell Biology, University of California, Berkeley 94720-3204, USA.
Kwan
J
J
Martin
G S
GS
D000818:Animals; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D002461:Cell Line, Transformed; D002642:Chick Embryo; D004789:Enzyme Activation; D005799:Genes, Dominant; D019950:Mitogen-Activated Protein Kinase 1; D015689:Oncogene Protein p21(ras) / Q000235:genetics / Q000378:metabolism*; D015688:Oncogene Protein pp60(v-src) / Q000502:physiology*; D010766:Phosphorylation; D051381:Rats; D015398:Signal Transduction
D015688:Oncogene Protein pp60(v-src); D017871:Calcium-Calmodulin-Dependent Protein Kinases; D019950:Mitogen-Activated Protein Kinase 1; D015689:Oncogene Protein p21(ras)