Rey I, Taylor-Harris P, van Erp H, Hall A
Chester Beatty Laboratories, Institute of Cancer Research, London, UK.
Oncogene. 1994 Mar;9(3):685-92.
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.
在与ras相关的GTP结合蛋白超家族中，只有ras本身被证明可作为一种癌基因。然而，其他七种蛋白质与ras的氨基酸同源性超过50%，其中一种，即rap1A，已被证明可与ras GTP酶激活蛋白（ras-GAP）相互作用，并在过表达时抑制ras功能。在本文中，我们研究了ras的另一个近亲R-ras的生物学和生化活性。我们发现，在体外，R-ras与ras具有一些共同的活性；它可与ras-GAP的催化结构域、神经纤维瘤蛋白的GAP相关结构域以及丝氨酸/苏氨酸激酶c-raf相互作用。此外，当显微注射到瑞士3T3细胞中时，R-ras可刺激c-fos的表达。然而，与ras不同的是，R-ras不会在静止的成纤维细胞中诱导DNA合成或膜皱襞，也不会诱导非洲爪蟾卵母细胞成熟或PC12细胞分化。此外，我们发现，与rap1A不同，R-ras不会干扰ras刺激的基因转录。我们从这些实验中得出结论，尽管R-ras和ras具有一些生化活性，但它们控制着不同的生物学过程。
