Hakuno F, Hughes D A, Yamamoto M
Department of Biophysics and Biochemistry, School of Science, University of Tokyo, Hongo, Japan.
Genes Cells. 1996 Mar;1(3):303-15. doi: 10.1046/j.1365-2443.1996.27029.x.
Schizosaccharomyces pombe Ras1 regulates two downstream pathways, namely the Byr2/Byr1/Spk1 mitogen-activated protein kinase cascade and the Cdc42sp small G protein pathway. The former is relevant to mating and sporulation, whereas the latter is relevant to mating, cell growth and cell morphology. We addressed whether Ras1 has any additional role in the regulation of cell physiology.
Using a specific mutation in the effector region of Ras1, we isolated a high-copy-number suppressor of the mating deficiency caused by a decrease of the Ras1 activity. The isolated gene, named mra1, encodes a novel protein of 359 amino acids, which has apparent homologues in rice and budding yeast. Disruption of mra1 indicated that it is essential for cell growth, and mutational analysis indicated that it is required for the promotion of mating. These two functions could be separated by mutations, suggesting that Mra1 is bifunctional. Overexpression of mra1 could also suppress the mating inefficiency caused by either overexpression of gap1, which is a downregulator of Ras1, or loss of function of zfs1, which is a gene relevant to the mating pheromone signalling. However, it could not suppress null mutations in genes involved in the two known pathways downstream of Ras1.
Mra1 is an apparent downstream factor of Ras1, which is essential for cell growth and relevant to mating but is not involved in the maintenance of cell morphology. Mra1 is unlikely to interact directly with the known pathways downstream of Ras1, implying that it may be a factor constituting a third pathway regulated by Ras1.
粟酒裂殖酵母Ras1调控两条下游通路,即Byr2/Byr1/Spk1丝裂原活化蛋白激酶级联反应和Cdc42sp小G蛋白通路。前者与交配和孢子形成有关,而后者与交配、细胞生长和细胞形态有关。我们研究了Ras1在细胞生理调节中是否具有其他作用。
利用Ras1效应区的特定突变,我们分离出一个高拷贝数的抑制子,可抑制因Ras1活性降低导致的交配缺陷。分离出的基因命名为mra1,编码一种由359个氨基酸组成的新蛋白,该蛋白在水稻和芽殖酵母中具有明显的同源物。mra1的破坏表明它对细胞生长至关重要,突变分析表明它是促进交配所必需的。这两种功能可以通过突变分开,表明Mra1具有双功能。mra1的过表达也可以抑制由gap1(Ras1的下调因子)过表达或zfs1(与交配信息素信号传导相关的基因)功能丧失引起的交配效率低下。然而,它不能抑制Ras1下游两条已知通路中基因的无效突变。
Mra1是Ras1明显的下游因子,对细胞生长至关重要且与交配相关,但不参与细胞形态的维持。Mra1不太可能直接与Ras1下游的已知通路相互作用,这意味着它可能是构成由Ras1调控的第三条通路的一个因子。