A SYNTHETIC LETHAL SCREEN IDENTIFIES SLK1, A NOVEL PROTEIN-KINASE HOMOLOG IMPLICATED IN YEAST-CELL MORPHOGENESIS AND CELL-GROWTH
A SYNTHETIC LETHAL SCREEN IDENTIFIES SLK1, A NOVEL PROTEIN-KINASE HOMOLOG IMPLICATED IN YEAST-CELL MORPHOGENESIS AND CELL-GROWTH
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DOI：
10.1128/mcb.12.3.1162
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发表时间：
1992-03-01
影响因子：
5.3
通讯作者：
SNYDER, M
中科院分区：
文献类型：
--
作者：
COSTIGAN, C;GEHRUNG, S;SNYDER, M
酿酒酵母SPA2蛋白定位于萌芽细胞和交配细胞中参与细胞极化生长的部位。Spa2突变体在交配过程中存在突起形成缺陷，但在营养生长过程中是健康的。设计了一种人工致死筛选来鉴定需要SPA2基因来进行营养生长的突变体。一种名为slk1-1(合成致死激酶的缩写)的突变体已经被广泛研究。SLK1基因已被克隆，序列分析预测SLK1蛋白全长1,478个氨基酸。大约有300个氨基酸的羧基末端与蛋白激酶的催化区序列相似。已经在SLK1基因中构建了破坏性突变。Slk1缺失突变体不能在37摄氏度生长，但许多细胞可以在30、24和17摄氏度生长。死亡的slk1突变细胞通常具有异常的细胞形态，许多细胞非常小，大约是野生型细胞直径的一半。幸存的slk1细胞也表现出形态发生缺陷；这些细胞在接触交配信息素时形成投射的能力受到损害。在营养生长过程中，与野生型细胞相比，较高比例的slk1细胞没有出芽，在营养限制条件下，slk1细胞表现出细胞周期停滞的缺陷。SSD1/SRK1基因的额外拷贝部分挽救了不同的slk1突变缺陷。SSD1/SRK1已经被独立地分离出来，作为参与生长控制的基因Sit4、pde2、bcy1和ins1的突变抑制因子(A.Sutton，D.Immanuel和K.T.Arnat，Mol.牢房。比奥尔。11：2133-2148,1991；R·B·威尔逊、A·A·布伦纳、T·B·怀特、M·J·恩格勒、J·P·高兰和K·塔切尔，摩尔。牢房。比奥尔。11：3369-3373,1991)。这些数据表明，SLK1在细胞形态发生和细胞生长控制中发挥作用。我们推测SLK1可能是这两个细胞过程的调节链。
The Saccharomyces cerevisiae SPA2 protein localizes at sites involved in polarized cell growth in budding cells and mating cells. spa2 mutants have defects in projection formation during mating but are healthy during vegetative growth. A synthetic lethal screen was devised to identify mutants that require the SPA2 gene for vegetative growth. One mutant, called slk1-1 (for synthetic lethal kinase), has been characterized extensively. The SLK1 gene has been cloned, and sequence analysis predicts that the SLK1 protein is 1,478 amino acid residues in length. Approximately 300 amino acids at the carboxy terminus exhibit sequence similarity with the catalytic domains of protein kinases. Disruption mutations have been constructed in the SLK1 gene. slk1 null mutants cannot grow at 37-degrees-C, but many cells can grow at 30, 24, and 17-degrees-C. Dead slk1 mutant cells usually have aberrant cell morphologies, and many cells are very small, approximately one-half the diameter of wild-type cells. Surviving slk1 cells also exhibit morphogenic defects; these cells are impaired in their ability to form projections upon exposure to mating pheromones. During vegetative growth, a higher fraction of slk1 cells are unbudded compared with wild-type cells, and under nutrient limiting conditions, slk1 cells exhibit defects in cell cycle arrest. The different slk1 mutant defects are partially rescued by an extra copy of the SSD1/SRK1 gene. SSD1/SRK1 has been independently isolated as a suppressor of mutations in genes involved in growth control, sit4, pde2, bcy1, and ins1 (A. Sutton, D. Immanuel, and K. T. Arnat, Mol. Cell. Biol. 11:2133-2148, 1991; R. B. Wilson, A. A. Brenner, T. B. White, M. J. Engler, J. P. Gaughran, and K. Tatchell, Mol. Cell. Biol. 11:3369-3373, 1991). These data suggest that SLK1 plays a role in both cell morphogenesis and the control of cell growth. We speculate that SLK1 may be a regulatory link for these two cellular processes.