Downward J, Riehl R, Wu L, Weinberg R A
Whitehead Institute for Biomedical Research, Cambridge, MA 02142.
Proc Natl Acad Sci U S A. 1990 Aug;87(15):5998-6002. doi: 10.1073/pnas.87.15.5998.
The biological activity of proteins encoded by the ras family of oncogenes is dependent on whether they are bound to GTP or GDP: the type of nucleotide bound is dependent on the rate of GTP hydrolysis (promoted by the GTPase-activating protein, GAP) and the rate of nucleotide exchange with cytosolic pools. A protein that stimulates the rate of exchange of guanine nucleotide on p21ras has been identified and characterized in cytoplasmic extracts of human placenta. The exchange-promoting protein runs on a gel filtration column with an apparent relative molecular weight of about 60,000. It is sensitive to heat and to trypsin. The exchange-promoting protein acts reversibly and does not cause degradation of p21ras. It is inactive towards the alpha subunit of a heterotrimeric GTP-binding protein (Go alpha) but acts on a large number of different mutant ras proteins, including transforming and effector mutants that are insensitive to the action of GAP. This protein, which we have termed REP (ras exchange-promoting), has the characteristics expected of a physiological activator of p21ras in cellular growth-signal-transduction pathways.
癌基因ras家族所编码蛋白质的生物活性取决于它们是与GTP还是GDP结合：所结合的核苷酸类型取决于GTP水解的速率（由GTP酶激活蛋白GAP促进）以及与胞质库进行核苷酸交换的速率。在人胎盘的细胞质提取物中已鉴定并表征了一种能刺激p21ras上鸟嘌呤核苷酸交换速率的蛋白质。促进交换的蛋白质在凝胶过滤柱上的表观相对分子质量约为60,000。它对热和胰蛋白酶敏感。促进交换的蛋白质作用是可逆的，不会导致p21ras降解。它对异三聚体GTP结合蛋白（Goα）的α亚基无活性，但作用于大量不同的突变ras蛋白，包括对GAP作用不敏感的转化型和效应型突变体。这种我们称为REP（ras交换促进蛋白）的蛋白质具有细胞生长信号转导途径中p21ras生理激活剂所预期的特征。
