Implication of GAP in Ras-dependent transactivation of a polyoma enhancer sequence.
Controversy exists as to whether the interaction of a guanosine triphosphatase activating protein (GAP) with Ras proteins functions both to initiate and to terminate Ras-dependent signaling events or only to terminate them. GAP-C, a carboxyl-terminal fragment of GAP that is sufficient to stimulate GTPase activity, inhibited the stimulation of transcription produced by some oncoproteins (v-Src, polyoma middle T, wild-type Ras, and oncogenic Ras) but not that produced by v-Mos. Wild-type GAP did not affect transcription induced by oncogenic Ras but reversed the inhibitory effect of GAP-C on transcription induced by oncogenic Ras. These results indicate that GAP is a negative regulator of wild-type Ras and elicits a downstream signal by interacting with Ras-GTP (guanosine triphosphate).
Schweighoffer
F
F
Rhône-Poulenc Rorer, Centre de Recherche de Vitry-Alfortville, Vitry Sur Seine.
Barlat
I
I
Chevallier-Multon
M C
MC
Tocque
B
B
D016475:3T3 Cells; D000818:Animals; D000952:Antigens, Polyomavirus Transforming / Q000235:genetics; D016466:CHO Cells; D018797:Cell Cycle Proteins; D002471:Cell Transformation, Neoplastic; D015500:Chloramphenicol O-Acetyltransferase / Q000235:genetics / Q000378:metabolism; D006224:Cricetinae; D004742:Enhancer Elements, Genetic; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism; D020690:GTPase-Activating Proteins; D011905:Genes, ras; D006801:Humans; D051379:Mice; D017232:Oncogene Proteins v-mos; D009857:Oncogenes; D011120:Polyomavirus / Q000235:genetics*; D011401:Promoter Regions, Genetic; D011505:Protein-Tyrosine Kinases / Q000235:genetics; D011506:Proteins / Q000378:metabolism*; D015682:Retroviridae Proteins, Oncogenic / Q000235:genetics; D015398:Signal Transduction; D013539:Simian virus 40 / Q000235:genetics; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D014162:Transfection; D020703:ras GTPase-Activating Proteins; D020666:ras-GRF1
D000952:Antigens, Polyomavirus Transforming; D018797:Cell Cycle Proteins; D005656:Fungal Proteins; D020690:GTPase-Activating Proteins; D017232:Oncogene Proteins v-mos; D011506:Proteins; D015682:Retroviridae Proteins, Oncogenic; D020703:ras GTPase-Activating Proteins; D020666:ras-GRF1; D015500:Chloramphenicol O-Acetyltransferase; D011505:Protein-Tyrosine Kinases