PKCε is a unique regulator for hsp90β gene in heat shock response

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 Go6976, specifically repressed heat shock-induced accumulation of mRNA as well as promoter activity of hsp90beta, but not hsp90alpha, 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 hsp90beta 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 hsp90beta expression seems to be stimuli-specific, as phorbol myristate acetate-mediated hsp90beta expression was PKC-epsilon-independent. We conclude that PKC-epsilon is specifically required in the signaling pathway leading to the induction of hsp90beta gene in response to heat shock.