Mechanistic aspects of signaling through Ras in NIH 3T3 cells.
Serum and growth factors can increase the proportion of Ras in the active guanosine triphosphate (GTP)-bound form. Growth factors might stimulate guanine nucleotide exchange or decrease the activity of the guanosine triphosphatase-activating proteins GAP and neurofibromin (NF1). In NIH 3T3 cells that overexpress the mutant Ras protein His116, which releases bound guanine nucleotide at a constitutively high rate and retains sensitivity to GAP and NF1, the proportion of GTP bound to the His116 protein was not altered by serum or platelet-derived growth factor. However, these mitogens increased the proportion of Ras in the GTP-bound form in cells that overexpressed control Ras proteins with a normal intrinsic rate of guanine nucleotide release. The amount of GTP-bound His116 or control Ras proteins was higher in cells at low density than in cells at high density, which have more GAP-like activity. The lower proportion of GTP-bound Ras in NIH 3T3 cells at high density may result from increased GAP-like activity. By contrast, serum and platelet-derived growth factors appear to stimulate guanine nucleotide exchange.
Zhang
K
K
Laboratory of Cellular Oncology, National Cancer Institute, Bethesda, MD 20892.
Papageorge
A G
AG
Lowy
D R
DR
D016475:3T3 Cells; D000818:Animals; D001769:Blood; D002461:Cell Line, Transformed; D005347:Fibroblasts / Q000378:metabolism*; D020690:GTPase-Activating Proteins; D015870:Gene Expression; D011905:Genes, ras / Q000502:physiology*; D006133:Growth Substances / Q000494:pharmacology*; D006160:Guanosine Triphosphate / Q000378:metabolism*; D006639:Histidine; D008715:Methionine; D051379:Mice; D016296:Mutagenesis; D025542:Neurofibromin 1; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D011506:Proteins / Q000494:pharmacology; D016283:Proto-Oncogene Proteins p21(ras) / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics*; D020703:ras GTPase-Activating Proteins
D020690:GTPase-Activating Proteins; D006133:Growth Substances; D025542:Neurofibromin 1; D010982:Platelet-Derived Growth Factor; D011506:Proteins; D020703:ras GTPase-Activating Proteins; D006639:Histidine; D006160:Guanosine Triphosphate; D008715:Methionine; D016283:Proto-Oncogene Proteins p21(ras)