Baker's yeast as a tool for the development of antifungal kinase inhibitors - targeting protein kinase C and the cell integrity pathway
Baker's yeast as a tool for the development of antifungal kinase inhibitors - targeting protein kinase C and the cell integrity pathway
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DOI：
10.1016/j.bbapap.2005.07.032
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发表时间：
2005-12-30
影响因子：
3.2
通讯作者：
Heinisch, JJ
中科院分区：
文献类型：
--
作者：
Heinisch, JJ
今天，酿酒酵母可能是研究得最好的真核生物。本文综述了酵母蛋白激酶C（Pkc 1 p）及其下游丝裂原活化蛋白激酶（MAPK）级联反应介导的信号转导过程。该途径通过感知细胞表面压力并控制细胞壁生物合成和细胞周期的进展来确保细胞完整性。Pkc 1 p的结构域结构从酵母到人类都是保守的。描述了用于嵌合酵母/哺乳动物PKC酶中特定结构域的异源表达（“结构域改组”）的酵母系统。它也提出了该系统如何可以用于蛋白激酶抑制剂的高通量筛选研究。此外，引入了允许定量读出细胞完整性信号传导途径的活性的报告基因测定。由于多种蛋白激酶参与信号转导，这拓宽了潜在抑制剂的靶点范围。(c)2005 Elsevier B. V.保留所有权利。
Today, the yeast Saccharomyces cerevisiae is probably the best-studied eukaryotic organism. This review first focusses on the signaling process which is mediated by the unique yeast protein kinase C (Pkc1p) and a downstream mitogen-activated protein kinase (MAPK) cascade. This pathway ensures cellular integrity by sensing cell surface stress and controlling cell wall biosynthesis and progression through the cell cycle. The domain structure of Pkc1p is conserved from yeast to humans. A yeast system for heterologous expression of specific domains in a chimeric yeast/mammalian PKC enzyme ("domain shuffling") is depicted. It is also proposed how this system could be employed for the study of protein kinase inhibitors in high-throughput screens. Moreover, a reporter assay that allows a quantitative readout of the activity of the cell integrity signaling pathway is introduced. Since a variety of protein kinases take part in the signal transduction, this broadens the range of targets for potential inhibitors. (c) 2005 Elsevier B.V. All rights reserved.