Santos J L, Shiozaki K
Biochemistry and Molecular Biology Graduate Program, University of California, Davis, CA 95616, USA.
Sci STKE. 2001 Sep 4;2001(98):re1. doi: 10.1126/stke.2001.98.re1.
Eukaryotic cells predominantly use serine, threonine, and tyrosine phosphorylation in various intracellular signal transduction pathways. In contrast, prokaryotic organisms employ numerous "two-component" systems, in which signaling is achieved by transferring a phosphoryl group from phosphohistidine in the "sensor kinase" component to aspartate in the "response regulator" component. In the last several years, genetic screens and genome projects have identified sensor kinases and response regulators in lower eukaryotes and plants, revealing that eukaryotic organisms also make use of His-Asp phosphotransfer in a limited number of signaling pathways. Extensive studies in yeasts have demonstrated that a variation of the two-component system, a multistep "phosphorelay," is the prevailing mechanism among distantly related yeast species. In the budding yeast Saccharomyces cerevisiae, a His-Asp-His-Asp phosphorelay transmits osmotic stress signals to a mitogen-activated protein kinase (MAPK) cascade to induce adaptive responses. A phosphorelay in the fission yeast Schizosaccharomyces pombe, analogous to the S. cerevisiae phosphorelay, is responsible for MAPK activation in response to peroxide stress. Mammalian cells do not have any two-component or phosphorelay systems, although protein histidine kinases unrelated to the sensor kinase may be involved in cellular signaling. Because some phosphorelay proteins are essential for virulence of microbial pathogens, including the yeast fungus Candida albicans, novel antibiotics targeted to phosphorelays may be effective against eukaryotic pathogens without causing host cell damage.
真核细胞在各种细胞内信号转导途径中主要使用丝氨酸、苏氨酸和酪氨酸磷酸化。相比之下，原核生物采用众多的“双组分”系统，其中信号传导是通过将磷酸组氨酸从“传感激酶”组分转移到“反应调节因子”组分中的天冬氨酸来实现的。在过去几年中，遗传筛选和基因组计划已在低等真核生物和植物中鉴定出传感激酶和反应调节因子，这表明真核生物在有限数量的信号传导途径中也利用组氨酸-天冬氨酸磷转移。对酵母的广泛研究表明，双组分系统的一种变体，即多步“磷中继”，是远缘酵母物种中的主要机制。在芽殖酵母酿酒酵母中，组氨酸-天冬氨酸-组氨酸-天冬氨酸磷中继将渗透胁迫信号传递给丝裂原活化蛋白激酶（MAPK）级联以诱导适应性反应。裂殖酵母粟酒裂殖酵母中的磷中继类似于酿酒酵母中的磷中继，负责在过氧化物胁迫下激活MAPK。哺乳动物细胞没有任何双组分或磷中继系统，尽管与传感激酶无关的蛋白质组氨酸激酶可能参与细胞信号传导。由于一些磷中继蛋白对于包括白色念珠菌酵母真菌在内的微生物病原体的毒力至关重要，因此针对磷中继的新型抗生素可能对真核病原体有效而不会对宿主细胞造成损害。
