Systematic deletion analysis of fission yeast protein kinases
Systematic deletion analysis of fission yeast protein kinases
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DOI：
10.1128/ec.4.4.799-813.2005
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发表时间：
2005-04-01
期刊：
影响因子：
--
通讯作者：
Liu, JH
中科院分区：
文献类型：
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作者：
Bimbó, A;Jia, YH;Liu, JH
真核蛋白激酶是介导信号转导的关键分子，其在各种生物过程的调节中发挥关键作用，包括细胞周期进展、细胞形态发生、发育和细胞对环境变化的响应。在整个裂殖酵母基因组中共发现了106种含有真核蛋白激酶催化结构域的蛋白质，其中44%（或64%）具有人类的直系同源物（或最接近的同源物），基于催化结构域内的序列相似性。系统缺失分析所有推定的蛋白激酶编码基因显示，106个中有17个是必需的生存能力，包括三个以前未知的推定蛋白激酶。虽然剩余的89个蛋白激酶突变体能够在最佳生长条件下形成菌落，但46%的突变体对测试的17种不同应激因子中的至少1种表现出超敏反应。这些突变体的表型评估使我们能够安排激酶功能组。基于该测定的结果，我们还提出了四个主要的信号通路的存在，这些信号通路参与了对测试的17种应力的响应。微阵列分析表明，测试的激酶突变体的表达签名和生长表型之间的显着相关性。我们完整的微阵列数据集可在http://giscompute.gis.a-star.edu.sg/similar上获得，网址为gisljh/kinome。
Eukaryotic protein kinases are key molecules mediating signal transduction that play a pivotal role in the regulation of various biological processes, including cell cycle progression, cellular morphogenesis, development, and cellular response to environmental changes. A total of 106 eukaryotic protein kinase catalytic-domain-containing proteins have been found in the entire fission yeast genome, 44% (or 64%) of which possess orthologues (or nearest homologues) in humans, based on sequence similarity within catalytic domains. Systematic deletion analysis of all putative protein kinase-encoding genes have revealed that 17 out of 106 were essential for viability, including three previously uncharacterized putative protein kinases. Although the remaining 89 protein kinase mutants were able to form colonies under optimal growth conditions, 46% of the mutants exhibited hypersensitivity to at least 1 of the 17 different stress factors tested. Phenotypic assessment of these mutants allowed us to arrange kinases into functional groups. Based on the results of this assay, we propose also the existence of four major signaling pathways that are involved in the response to 17 stresses tested. Microarray analysis demonstrated a significant correlation between the expression signature and growth phenotype of kinase mutants tested. Our complete microarray data sets are available at http://giscompute.gis.a-star.edu.sg/similar to gisljh/kinome.