Louvion J F, Abbas-Terki T, Picard D
Département de Biologie Cellulaire, Université de Genève Sciences III, CH-1211 Genève 4, Switzerland.
Mol Biol Cell. 1998 Nov;9(11):3071-83. doi: 10.1091/mbc.9.11.3071.
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 Hsp90beta 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, Ste11 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 Hsp90beta 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.
热休克蛋白90（Hsp90）是一种胞质分子伴侣，即使在常温下也高度丰富。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）相互作用的特性，人们提出了Hsp90的特定功能。因此，我们决定研究Hsp90在芽殖酵母的丝裂原活化蛋白激酶（MAP）激酶途径中的作用，芽殖酵母是一种适合进行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均依赖于Hsp90。在表达低水平酵母Hsp90（Hsp82）或其点突变体，或表达人Hsp90β而非野生型蛋白的菌株中，信号传导存在缺陷。酵母中与Raf等效的Ste11与野生型Hsp90形成复合物，并且其积累依赖于Hsp90的功能。对于芽殖酵母而言，Ste11是首个被鉴定出的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在遗传上是可分离的，因为Hsp82点突变体T525I和人Hsp90β分别对前者和后者存在特异性缺陷。这些发现进一步证实了以下观点，即分子伴侣也必须被视为信号转导途径的瞬时或稳定组分。
