PKC epsilon is a unique regulator for hsp90 beta gene in heat shock response.
PKC epsilon is a unique regulator for hsp90 beta gene in heat shock response.
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发表时间：
2003
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通讯作者：
Jian-min Wu;Lei Xiao;Xiao-kuan Cheng;Lian-Xian Cui;N. Wu;Yu‐fei Shen
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作者：
Jian-min Wu;Lei Xiao;Xiao-kuan Cheng;Lian-Xian Cui;N. Wu;Yu‐fei Shen
细胞热休克反应的早期事件是应激信号从细胞表面传递到细胞核，导致热休克蛋白（Hsps）的诱导。蛋白激酶C（PKC）是介导应激信号转导的关键分子。然而，PKC调节热休克诱导事件的机制在很大程度上仍然未知。在这里，我们提出的数据，泛蛋白激酶C抑制剂GF 109203 X，但不是经典的蛋白激酶C抑制剂Gö 6976，特别是抑制热休克诱导的mRNA的积累，以及启动子活性的热休克蛋白90 β，但不是热休克蛋白90 α，在Jurkat细胞。亚细胞分级分离研究表明，热休克只诱导PKC-β膜转位。一致的是，组成型活性的PKC-β（A159 E）的表达导致热休克后hsp 90 β的启动子活性增强，而显性负性PKC-β（K437 R）消除了这种作用。相比之下，组成性激活的PKC-α或显性负性PKC-α对该基因的热休克诱导没有影响。PKC β对hsp 90 β表达的影响似乎是刺激特异性的，因为佛波酯肉豆蔻酸酯介导的hsp 90 β表达是PKC β非依赖性的。我们的结论是，PKC-β是特别需要的信号通路导致热休克反应的hsp 90 β基因的诱导。
An early event in cellular heat shock response is the transmittance of stress signals from the cell surface into the nuclei, resulting in the induction of heat shock proteins (Hsps). Protein kinase C (PKC) has been implicated as a key player in transducing stress signals. However, mechanism(s) by which PKC regulates heat shock-induced events remains largely unknown. Here we present data that pan-PKC inhibitor GF109203X, but not classic PKC inhibitor Gö6976, specifically repressed heat shock-induced accumulation of mRNA as well as promoter activity of hsp90 beta, but not hsp90 alpha, in Jurkat cells. Subcellular fractionation studies revealed that heat shock exclusively induced PKC-epsilon membrane translocation. Consistently, expression of a constitutively active PKC-epsilon(A159E) resulted in an enhanced promoter activity of hsp90 beta upon heat shock, whereas a dominant-negative PKC-epsilon(K437R) abolished this effect. In contrast, constitutively active-PKC-alpha or dominant-negative-PKC-alpha had no effects on heat shock induction of the gene. The effect of PKC-epsilon on hsp90 beta expression seems to be stimuli-specific, as phorbol myristate acetate-mediated hsp90 beta expression was PKC-epsilon-independent. We conclude that PKC-epsilon is specifically required in the signaling pathway leading to the induction of hsp90 beta gene in response to heat shock.