LOSS OF RAS ACTIVITY IN SACCHAROMYCES-CEREVISIAE IS SUPPRESSED BY DISRUPTIONS OF A NEW KINASE GENE, YAKI, WHOSE PRODUCT MAY ACT DOWNSTREAM OF THE CAMP-DEPENDENT PROTEIN-KINASE
LOSS OF RAS ACTIVITY IN SACCHAROMYCES-CEREVISIAE IS SUPPRESSED BY DISRUPTIONS OF A NEW KINASE GENE, YAKI, WHOSE PRODUCT MAY ACT DOWNSTREAM OF THE CAMP-DEPENDENT PROTEIN-KINASE
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DOI：
10.1101/gad.3.9.1336
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发表时间：
1989-09-01
影响因子：
10.5
通讯作者：
BROACH, J
中科院分区：
文献类型：
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作者：
GARRETT, S;BROACH, J
酵母含有两个功能冗余基因RAS1和RAS2，这两个基因与哺乳动物ras基因家族同源，是营养生长所必需的。我们分离并鉴定了RAS2的5个温度敏感等位基因。在ras1菌株中，这些等位基因在细胞周期的GI阶段引起生长停滞。能够在非允许温度下生长的复合体定义了四个隐性的，基因外的互补基团。一个互补组（指定为yak1）中的抑制子特别有趣，因为它们似乎只减轻温度敏感的ras突变体的生长缺陷，而不表现出任何表型，例如与cAMP产量增加相关的热休克敏感性或饥饿敏感性。YAK1基因已被克隆，在体外产生的破坏表明，它不是生长所必需的，它的缺失使tpk1、tpk2和tpk3缺失的菌株生长，tpk1、tpk2和tpk3是camp依赖性蛋白激酶催化亚基的结构基因。这些结果将Yak1置于Ras/cAMP通路中激酶步骤的下游或平行通路上。最后，编码区预测了一个与蛋白激酶家族具有显著同源性的蛋白，这表明camp依赖性蛋白激酶功能的丧失可以通过第二个蛋白激酶的丧失来抑制。
The yeast Saccharomyces cerevisiae contains two functionally redundant genes RAS1 and RAS2, which are homologous to the mammalian ras gene family and are required for vegetative growth. We isolated and characterized five temperature-sensitive alleles of RAS2. In a ras1 strain, these alleles cause growth arrest at the GI stage of the cell cycle. Revertants capable of growth at the nonpermissive temperature define four recessive, extragenic complementation groups. Suppressors in one complementation group (designated yak1) are particularly intriguing because they appear to alleviate only the growth defect of the temperature-sensitive ras mutants and do not show any of the phenotypes, such as heat shock sensitivity of starvation sensitivity, associated with increased production of cAMP. The YAK1 gene has been cloned, and disruptions generated in vitro reveal that it is not essential for growth and that its loss confers growth to a strain deleted for tpk1, tpk2, and tpk3, the structural genes for the catalytic subunit of the cAMP-dependent protein kinase. These results place Yak1 downstream from, or on a parallel pathway to, the kinase step in the Ras/cAMP pathway. Finally, the coding region predicts a protein with significant homology to the family of protein kinases, suggesting that loss of cAMP-dependent protein kinase function can be suppressed by the loss of a second protein kinase.