Hsp90 is required for pheromone signaling in yeast
Hsp90 is required for pheromone signaling in yeast
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DOI：
10.1091/mbc.9.11.3071
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发表时间：
1998-11-01
影响因子：
3.3
通讯作者：
Picard, D
中科院分区：
文献类型：
--
作者：
Louvion, JF;Abbas-Terki, T;Picard, D
热休克蛋白 90 (Hsp90) 是一种胞质分子伴侣，即使在常温下也含量很高。 Hsp90 的特定功能是基于其与某些转录因子和激酶（包括脊椎动物和果蝇中的 Raf）相互作用的表征而提出的。因此，我们决定研究 Hsp90 在芽殖酵母中 MAP 激酶通路中的作用，芽殖酵母是一种适合遗传和生化分析的生物体。我们发现信息素信号通路的基础活性和诱导活性都依赖于 Hsp90。在表达低水平或点突变的酵母 Hsp90 (Hsp82) 或人 Hsp90 beta（而不是野生型蛋白）的菌株中，信号传导存在缺陷。 Ste11 是 Raf 的酵母等价物，与野生型 Hsp90 形成复合物，并依赖 Hsp90 功能进行积累。对于出芽酵母，失速。代表第一个鉴定的 Hsp90 内源性“底物”。此外，Hsp90 在类固醇受体和信息素信号传导中的功能可以在基因上分离，因为 Hsp82 点突变体 T525I 和人 Hsp90 beta 分别对前者和后者有特异性缺陷。这些发现进一步证实了分子伴侣也必须被视为信号转导途径的瞬时或稳定成分的观点。
The heat-shock protein 90 (Hsp90) is a cytosolic molecular chaperone that is highly abundant even at normal temperature. Specific functions for Hsp90 have been proposed based on the characterization of its interactions with certain transcription factors and kinases including Raf in vertebrates and flies. We therefore decided to address the role of Hsp90 for MAP kinase pathways in the budding yeast, an organism amenable to both genetic and biochemical analyses. We found that both basal and induced activities of the pheromone-signaling pathway depend on Hsp90. Signaling is defective in strains expressing low levels or point mutants of yeast Hsp90 (Hsp82), or human Hsp90 beta instead of the wild-type protein. Ste11, a yeast equivalent of Raf, forms complexes with wild-type Hsp90 and depends on Hsp90 function for accumulation. For budding yeast, Stall. represents the first identified endogenous "substrate" of Hsp90. Moreover, Hsp90 functions in steroid receptor and pheromone signaling can be genetically separated as the Hsp82 point mutant T525I and the human Hsp90 beta are specifically defective for the former and the latter, respectively. These findings further corroborate the view that molecular chaperones must also be considered as transient or stable components of signal transduction pathways.