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酿酒酵母中cAMP-蛋白激酶A途径的新型传感机制和靶点

Novel sensing mechanisms and targets for the cAMP-protein kinase A pathway in the yeast Saccharomyces cerevisiae.

作者信息

Thevelein J M, de Winde J H

机构信息

Laboratorium voor Moleculaire Celbiologie, Katholieke Universiteit Leuven, Kardinaal Mercierlaan 92, B-3001 Leuven-Heverlee, Flanders, Belgium.

出版信息

Mol Microbiol. 1999 Sep;33(5):904-18. doi: 10.1046/j.1365-2958.1999.01538.x.

Abstract

The cAMP-protein kinase A (PKA) pathway in the yeast Saccharomyces cerevisiae plays a major role in the control of metabolism, stress resistance and proliferation, in particular in connection with the available nutrient conditions. Extensive information has been obtained on the core section of the pathway, i.e. Cdc25, Ras, adenylate cyclase, PKA, and on components interacting directly with this core section, such as the Ira proteins, Cap/Srv2 and the two cAMP phosphodiesterases. Recent work has now started to reveal upstream regulatory components and downstream targets of the pathway. A G-protein-coupled receptor system (Gpr1-Gpa2) acts upstream of adenylate cyclase and is required for glucose activation of cAMP synthesis in concert with a glucose phosphorylation-dependent mechanism. Although a genuine signalling role for the Ras proteins remains unclear, they appear to mediate at least part of the potent stimulation of cAMP synthesis by intracellular acidification. Recently, several new targets of the PKA pathway have been discovered. These include the Msn2 and Msn4 transcription factors mediating part of the induction of STRE-controlled genes by a variety of stress conditions, the Rim15 protein kinase involved in stationary phase induction of a similar set of genes and the Pde1 low-affinity cAMP phosphodiesterase, which specifically controls agonist-induced cAMP signalling. A major issue that remains to be resolved is the precise connection between the cAMP-PKA pathway and other nutrient-regulated components involved in the control of growth and of phenotypic characteristics correlated with growth, such as the Sch9 and Yak1 protein kinases. Cln3 appears to play a crucial role in the connection between the availability of certain nutrients and Cdc28 kinase activity, but it remains to be clarified which nutrient-controlled pathways control Cln3 levels.

摘要

酿酒酵母中的环磷酸腺苷-蛋白激酶A(PKA)途径在代谢、应激抗性和增殖控制中起主要作用,特别是与可用营养条件相关。关于该途径的核心部分,即Cdc25、Ras、腺苷酸环化酶、PKA,以及与该核心部分直接相互作用的成分,如Ira蛋白、Cap/Srv2和两种环磷酸腺苷磷酸二酯酶,已经获得了大量信息。最近的研究现已开始揭示该途径的上游调节成分和下游靶点。一种G蛋白偶联受体系统(Gpr1-Gpa2)在腺苷酸环化酶上游起作用,并且与葡萄糖磷酸化依赖性机制协同作用,是葡萄糖激活环磷酸腺苷合成所必需的。尽管Ras蛋白的真正信号传导作用仍不清楚,但它们似乎至少介导了细胞内酸化对环磷酸腺苷合成的部分强效刺激。最近,发现了PKA途径的几个新靶点。这些包括Msn2和Msn4转录因子,它们介导多种应激条件下STRE控制基因诱导的部分过程;Rim15蛋白激酶参与一组类似基因的静止期诱导;以及Pde1低亲和力环磷酸腺苷磷酸二酯酶,它特异性地控制激动剂诱导的环磷酸腺苷信号传导。一个有待解决的主要问题是环磷酸腺苷-PKA途径与其他参与生长控制以及与生长相关的表型特征控制的营养调节成分之间的确切联系,例如Sch9和Yak1蛋白激酶。Cln3似乎在某些营养物质的可用性与Cdc28激酶活性之间的联系中起关键作用,但仍有待阐明哪些营养控制途径控制Cln3水平。

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