Polakis P, McCormick F
Cetus Corporation, Emeryville, California 94608.
Cancer Surv. 1992;12:25-42.
Two proteins that regulate p21ras GTPase activity have been identified. These proteins interact with a region of ras p21 that is necessary for p21ras function and may themselves be components of signalling complexes. The first of these proteins to be identified, GAP, contains domains that interact with receptor tyrosine kinases and other tyrosine phosphoproteins, providing a direct link between signalling pathways involving these proteins and p21ras. The second, the product of the NF1 gene, is less well characterized but seems to connect p21ras to other signalling pathways which are perturbed in the NF1 disease. The ability of p21ras to interact with GAP may be compromised by competitive binding to the product of the Ki-rev1 gene, p21rap1. This competition for binding to GAP, or other proteins that interact with the effector site of ras p21, may explain the ability of Ki-rev1 to suppress cellular transformation by ras oncogenes.
已鉴定出两种调节p21ras GTP酶活性的蛋白质。这些蛋白质与p21ras的一个区域相互作用，该区域对p21ras功能至关重要，并且它们自身可能是信号复合物的组成部分。首先被鉴定出的这种蛋白质是GAP，它含有与受体酪氨酸激酶和其他酪氨酸磷蛋白相互作用的结构域，在涉及这些蛋白质的信号通路与p21ras之间建立了直接联系。第二种是NF1基因的产物，其特征了解较少，但似乎将p21ras与NF1疾病中受到干扰的其他信号通路联系起来。p21ras与GAP相互作用的能力可能会因与Ki-rev1基因产物p21rap1的竞争性结合而受损。这种对与GAP或其他与ras p21效应位点相互作用的蛋白质的结合竞争，可能解释了Ki-rev1抑制ras癌基因诱导细胞转化的能力。
