PKCε Is a Unique Regulator for hsp90β Gene in Heat Shock Response

Abstract

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 hsp90β, but not hsp90α, in Jurkat cells. Subcellular fractionation studies revealed that heat shock exclusively induced PKC-ε membrane translocation. Consistently, expression of a constitutively active PKC-ε(A159E) resulted in an enhanced promoter activity of hsp90β upon heat shock, whereas a dominant-negative PKC-ε(K437R) abolished this effect. In contrast, constitutively active-PKC-α or dominant-negative-PKC-α had no effects on heat shock induction of the gene. The effect of PKC-ε on hsp90β expression seems to be stimuli-specific, as phorbol myristate acetate-mediated hsp90β expression was PKC-ε-independent. We conclude that PKC-ε is specifically required in the signaling pathway leading to the induction of hsp90β gene in response to heat shock.