Cross-talk between protein kinase C-alpha (PKC-alpha) and -delta (PKC-delta): PKC-alpha elevates the PKC-delta protein level, altering its mRNA transcription and degradation.
Cross-talk between protein kinase C-alpha (PKC-alpha) and -delta (PKC-delta): PKC-alpha elevates the PKC-delta protein level, altering its mRNA transcription and degradation.
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蛋白激酶 C-α (PKC-α) 和 -δ (PKC-delta) 之间的串扰：PKC-α 提高 PKC-delta 蛋白水平，改变其 mRNA 转录和降解。
作者：
L. Romanova;Ivan A. Alexandrov;Richard P. Nordan;Mikhail V. Blagosklonny;J. Mushinski
利用单个亚型的过表达的研究表明，PKC-α和-δ都促进了许多生物学效应，包括抑制与小鼠B细胞淋巴瘤（Baf 3）中肌动蛋白细胞骨架重排相关的DNA合成，小鼠早幼粒细胞系32 D的分化，以及CHO成纤维细胞中MAP激酶的活化。我们假设这些结果反映了PKC-α和-δ之间的某种形式的交叉调节，而不是它们的功能冗余。在这份报告中，我们表明，PKC-α在Baf 3和32 D的过度表达导致内源性PKC-δ mRNA和蛋白水平的升高。升高的稳态PKC-δ mRNA水平由增加的PKC-δ转录和mRNA稳定性的组合引起。即使在选择性消耗PKC-δ蛋白后，PKC-α也会上调PKC-δ mRNA。此外，佛波酯诱导的PKC-δ mRNA和蛋白水平的升高可以通过PKC抑制剂GF 109203 X来预防，这表明需要PKC激酶活性。放线菌酮对新蛋白质合成的抑制表明，PKC-δ mRNA的上调，而不是PKC-δ蛋白的延迟下调，是PKC-α积累这种亚型的主要原因。在亲本Baf 3和32 D细胞和PKC-α过表达者中，PKC-α和PKC-δ独特地参与交叉调节，而PKC-β、PKC-eta和PKC-μ不参与。
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), 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-alpha and -delta rather than their 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 transcription and mRNA stability. Upregulation of PKC-delta mRNA by PKC-alpha occurs even after a selective depletion of the PKC-delta protein. In addition, 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 primarily responsible for the accumulation of this isoform by PKC-alpha. In parental Baf3 and 32D cells and PKC-alpha overexpressers, PKC-alpha and PKC-delta are uniquely involved in cross-regulation, while PKC-epsilon, PKC-eta, and PKC-mu are not.