Pratt W B, Silverstein A M, Galigniana M D
Department of Pharmacology, University of Michigan Medical School, Ann Arbor 48109, USA.
Cell Signal. 1999 Dec;11(12):839-51. doi: 10.1016/s0898-6568(99)00064-9.
A number of transcription factors and protein kinases involved in signal transduction exist in heterocomplexes with the ubiquitous and essential protein chaperone hsp90. These signalling protein x hsp90 heterocomplexes are assembled by a multiprotein chaperone system comprising hsp90, hsp70, Hop, hsp40, and p23. In the case of transcription factors, the heterocomplexes with hsp90 also contain a high molecular weight immunophilin with tetratricopeptide repeat (TPR) motifs, such as FKBP52 or CyP-40. In the case of the protein kinases, the heterocomplexes contain p50cdc37. The immunophilins bind to a single TPR acceptor site on hsp90, and p50cdc37 binds to an adjacent site so that binding is exclusive for p50cdc37 or an immunophilin. Direct interaction of immunophilins with the transcription factors or p50cdc37 with the protein kinases leads to selection of different heterocomplexes after their assembly by a common mechanism. Studies with the glucocorticoid receptor, for which translocation from the cytoplasm to the nucleus is under hormonal control, suggest that dynamic assembly of the heterocomplexes is required for rapid movement of the receptor through the cytoplasm along cytoskeletal tracts. As for the similar short-range trafficking of vesicles along microtubules, there must be a mechanism for linking the signalling protein solutes to the molecular motors involved in movement. We present here a model in which the immunophilins and p50cdc37 target, respectively, the retrograde or anterograde direction of signalling protein movement by functioning as connectors that link the signalling proteins to the movement machinery.
一些参与信号转导的转录因子和蛋白激酶与普遍存在且至关重要的蛋白伴侣hsp90形成异源复合物。这些信号蛋白x hsp90异源复合物由一个多蛋白伴侣系统组装而成，该系统包括hsp90、hsp70、Hop、hsp40和p23。就转录因子而言，与hsp90的异源复合物还包含一种具有四肽重复（TPR）基序的高分子量亲免蛋白，如FKBP52或CyP - 40。就蛋白激酶而言，异源复合物包含p50cdc37。亲免蛋白与hsp90上的单个TPR受体位点结合，p50cdc37与相邻位点结合，使得p50cdc37或亲免蛋白的结合是排他性的。亲免蛋白与转录因子的直接相互作用或p50cdc37与蛋白激酶的直接相互作用导致它们通过共同机制组装后选择不同的异源复合物。对糖皮质激素受体的研究表明，其从细胞质到细胞核的转运受激素控制，这表明异源复合物的动态组装是受体沿细胞骨架束在细胞质中快速移动所必需的。至于囊泡沿微管的类似短程运输，必须有一种机制将信号蛋白溶质与参与移动的分子马达联系起来。我们在此提出一个模型，其中亲免蛋白和p50cdc37分别作为将信号蛋白与移动机制联系起来的连接器，靶向信号蛋白移动的逆行或顺行方向。
