Temeles G L, Gibbs J B, D'Alonzo J S, Sigal I S, Scolnick E M
Nature. 1985;313(6004):700-3. doi: 10.1038/313700a0.
Mammalian ras oncogenes encode polypeptides of relative molecular mass (Mr) 21,000 (p21) which bind GTP and GDP. Oncogenic ras-encoded proteins differ from their normal homologues by an amino acid substitution for Gly 12, Ala 59 or Gln 61. Recently, we and others have observed that normal p21, encoded by the Ha-ras gene, has a GTP hydrolytic activity that is reduced by the oncogenic substitutions Val 12 or Thr 59. The yeast Saccharomyces cerevisiae contains two ras-related genes, RASsc1 and RASsc2, the expression of either of which is sufficient for viability. RASsc1 and RASsc2 encode proteins of 309 (SC1) and 322 (SC2) residues which are 62% homologous to mammalian p21 in their 172-amino acid N-terminal sequences. We report here that the N-terminal domain of SC1 binds GTP and GDP and has a GTP hydrolytic activity that is reduced in the variants SC1[Thr 66] and SC1[Leu 68] which are analogous to oncogenic Ha[Thr 59] and Ha[Leu 61], respectively. These results suggest that yeast and mammalian ras proteins have similar biochemical and possibly biological functions.
哺乳动物的ras癌基因编码相对分子质量（Mr）为21,000的多肽（p21），该多肽可结合GTP和GDP。致癌性ras编码的蛋白质与它们的正常同源物的区别在于第12位甘氨酸、第59位丙氨酸或第61位谷氨酰胺被氨基酸取代。最近，我们和其他人观察到，由Ha-ras基因编码的正常p21具有GTP水解活性，该活性会因致癌性取代Val 12或Thr 59而降低。酿酒酵母含有两个与ras相关的基因，RASsc1和RASsc2，其中任何一个基因的表达都足以维持细胞存活。RASsc1和RASsc2编码分别由309个（SC1）和322个（SC2）残基组成的蛋白质，它们在其172个氨基酸的N端序列中与哺乳动物p21有62%的同源性。我们在此报告，SC1的N端结构域结合GTP和GDP，并具有GTP水解活性，在分别类似于致癌性Ha[Thr 59]和Ha[Leu 61]的变体SC1[Thr 66]和SC1[Leu 68]中，该活性降低。这些结果表明酵母和哺乳动物的ras蛋白具有相似的生化功能，可能还具有相似的生物学功能。
