Cross-Talk between Protein Kinase C-α (PKC-α) and -δ (PKC-δ): PKC-α Elevates the PKC-δ Protein Level, Altering Its mRNA Transcription and Degradation

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Abstract
Studies utilizing the overexpression of individual isoforms indicated that both PKC-α and -δ 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), differentiation of the murine promyelocyte line 32D, and activation of MAP kinase in CHO fibroblasts. We postulated that these results reflect some form of cross-regulation between PKC-α and -δ rather than their functional redundancy. In this report, we show that overexpression of PKC-α in Baf3 and 32D leads to an elevation of the endogenous PKC-δ mRNA and protein levels. The elevated steady-state PKC-δ mRNA level results from a combination of increased PKC-δ transcription and mRNA stability. Upregulation of PKC-δ mRNA by PKC-α occurs even after a selective depletion of the PKC-δ protein. In addition, phorbol ester-induced elevation of PKC-δ 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-δ mRNA, as opposed to delayed downregulation of the PKC-δ protein, is primarily responsible for the accumulation of this isoform by PKC-α. In parental Baf3 and 32D cells and PKC-α overexpressers, PKC-α and PKC-δ are uniquely involved in cross-regulation, while PKC-ε, PKC-η, and PKC-μ are not.