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Identification of a GTPase-activating protein homolog in Schizosaccharomyces pombe.

机译:粟酒裂殖酵母中GTPase激活蛋白同源物的鉴定。

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Loss of function of the Schizosaccharomyces pombe gap1 gene results in the same phenotypes as those caused by an activated ras1 mutation, i.e., hypersensitivity to the mating factor and inability to perform efficient mating. Sequence analysis of gap1 indicates that it encodes a homolog of the mammalian Ras GTPase-activating protein (GAP). The predicted gap1 gene product has 766 amino acids with relatively short N- and C-terminal regions flanking the conserved core sequence of GAP. Genetic analysis suggests that S. pombe Gap1 functions primarily as a negative regulator of Ras1, like S. cerevisiae GAP homologs encoded by IRA1 and IRA2, but is unlikely to be a downstream effector of the Ras protein, a role proposed for mammalian GAP. Thus, Gap1 and Ste6, a putative GDP-GTP-exchanging protein for Ras1 previously identified, appear to play antagonistic roles in the Ras-GTPase cycle in S. pombe. Furthermore, we suggest that this Ras-GTPase cycle involves the ra12 gene product, another positive regulator of Ras1 whose homologs have not been identified in other organisms, which could function either as a second GDP-GTP-exchanging protein or as a factor that negatively regulates Gap1 activity.
机译:粟酒裂殖酵母gap1基因功能的丧失导致了与激活的ras1突变引起的表型相同的表型,即对交配因子的超敏性和无法进行有效交配。 gap1的序列分析表明,它编码哺乳动物的Ras GTPase激活蛋白(GAP)的同源物。预测的gap1基因产物具有766个氨基酸,其N和C端区域相对较短,位于GAP的保守核心序列旁。遗传分析表明,粟酒裂殖酵母Gap1主要充当Ras1的负调控因子,就像IRA1和IRA2编码的酿酒酵母GAP同源物一样,但不太可能是Ras蛋白的下游效应子,这是哺乳动物GAP的作用。因此,Gap1和Ste6,以前确定的Ras1假定的GDP-GTP交换蛋白,似乎在粟酒裂殖酵母的Ras-GTPase循环中起拮抗作用。此外,我们建议该Ras-GTPase循环涉及ra12基因产物,这是Ras1的另一种正向调节因子,其同源物尚未在其他生物中鉴定出来,它可能充当第二种GDP-GTP交换蛋白或负因子。调节Gap1活性。

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