CROSS-TALK BETWEEN PROTEIN-KINASE-C-ALPHA (PKC-ALPHA) AND PKC-DELTA (PKC-DELTA) - PKC-ALPHA ELEVATES THE PKC-DELTA PROTEIN LEVEL, ALTERING ITS MESSENGER-RNA TRANSCRIPTION AND DEGRADATION

Studies utilizing the overexpression of individual isoforms indicated that both PKC-alpha and -delta promote a number of biological effects, including inhibition of DNA synthesis associated with rearrangements of the actin cytoskeleton in the murine B-cell lymphoma (Baf3), differ entiation of the murine promyelocyte line 32D, and activation of MAP k inase in CHO fibroblasts. We postulated that these results reflect som e form of cross-regulation between PKC-alpha and -delta rather than th eir functional redundancy. In this report, we show that overexpression of PKC-alpha in Baf3 and 32D leads to an elevation of the endogenous PKC-delta mRNA and protein levels. The elevated steady-state PKC-delta mRNA level results from a combination of increased PKC-delta transcri ption and mRNA stability. Upregulation of PKC-delta mRNA by PKC-alpha occurs even after a selective depletion of the PKC-delta protein. In a ddition, phorbol ester-induced elevation of PKC-delta mRNA and protein levels can be prevented by the PKC inhibitor GF109203X, an indication of the requirement for PKC kinase activity. Inhibition of new protein synthesis by cycloheximide showed that upregulation of PKC-delta mRNA , as opposed to delayed downregulation of the PKC-delta protein, is pr imarily responsible for the accumulation of this isoform by PKC-alpha. In parental Baf3 and 32D cells and PKC-alpha overexpressers, PKC-alph a and PKC-delta are uniquely involved in cross-regulation, while PKC-e psilon, PKC-eta, and PKC-mu are not.