R-ras interacts with rasGAP, neurofibromin and c-raf but does not regulate cell growth or differentiation.
Within the superfamily of ras-related GTP-binding proteins, only ras itself has been shown to act as an oncogene. Seven other proteins, however, have greater than 50% amino acid identity to ras and one of them, rap1A, has been shown to interact with the ras GTPase activating protein, ras-GAP, and to inhibit ras function when overexpressed. In this paper, we have examined the biological and biochemical activities of another close relative of ras, R-ras. We show that in vitro, R-ras shares a number of activities with ras; it interacts with the catalytic domain of ras-GAP, with the GAP-related domain of neurofibromin and with the ser/thr kinase, c-raf. Furthermore, R-ras stimulates the expression of c-fos when microinjected into Swiss 3T3 cells. However, unlike ras, R-ras does not include DNA synthesis or membrane ruffling in quiescent fibroblasts, nor does it induce maturation of Xenopus oocytes or differentiation of PC12 cells. In addition, we show that unlike rap1A, R-ras does not interfere with ras-stimulated gene transcription. We conclude from these experiments that although R-ras and ras share some biochemical activities, they control distinct biological processes.
Rey
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I
Chester Beatty Laboratories, Institute of Cancer Research, London, UK.
Taylor-Harris
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P
van Erp
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Hall
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D016475:3T3 Cells; D000818:Animals; D001483:Base Sequence; D002454:Cell Differentiation; D002455:Cell Division; D002462:Cell Membrane / Q000378:metabolism; D018076:DNA, Complementary; D004742:Enhancer Elements, Genetic; D020558:GTP Phosphohydrolases / Q000378:metabolism*; D019204:GTP-Binding Proteins / Q000378:metabolism*; D020690:GTPase-Activating Proteins; D051379:Mice; D008969:Molecular Sequence Data; D025542:Neurofibromin 1; D016716:PC12 Cells; D011120:Polyomavirus / Q000235:genetics; D011506:Proteins / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D019908:Proto-Oncogene Proteins c-raf; D016283:Proto-Oncogene Proteins p21(ras) / Q000378:metabolism; D015533:Transcriptional Activation; D014981:Xenopus; D020703:ras GTPase-Activating Proteins; D018631:ras Proteins
D018076:DNA, Complementary; D020690:GTPase-Activating Proteins; D025542:Neurofibromin 1; D011506:Proteins; D011518:Proto-Oncogene Proteins; D020703:ras GTPase-Activating Proteins; D019908:Proto-Oncogene Proteins c-raf; D020558:GTP Phosphohydrolases; D019204:GTP-Binding Proteins; C513254:Rras protein, mouse; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins