Wang C, Constantinescu S N, MacEwan D J, Strulovici B, Dekker L V, Parker P J, Pfeffer L M
Department of Pathology, University of Tennessee Health Science Center, Memphis 38163.
Proc Natl Acad Sci U S A. 1993 Aug 1;90(15):6944-8. doi: 10.1073/pnas.90.15.6944.
Protein kinases play key roles in the induction by human interferon alpha (IFN-alpha) of specific gene expression and biological activity in various human cell lines. We now report that IFN-alpha increased the 7-kb transcript for the epsilon isotype of protein kinase C (PKC-epsilon) and the cellular content of PKC-epsilon 24 and 48 hr after IFN-alpha addition (a 2-fold and 6-fold increase, respectively). Furthermore, IFN-alpha markedly induced a 4.7-kb transcript that hybridized to a PKC-epsilon-specific, but not to a PKC-eta-specific, cDNA probe. The induction of the 4.7-kb PKC-epsilon-related mRNA by IFN-alpha had the following properties reported for the classical IFN-alpha-stimulated genes: rapid kinetics of induction, high maintained levels in IFN-alpha-sensitive but not in IFN-alpha-resistant cell lines, protein synthesis-independent induction, and high sensitivity to inhibitors of protein tyrosine kinase activity. These results show that the regulation of gene expression by IFN-alpha include not only the classical IFN-alpha-stimulated genes but also the coordinated regulation of two PKC-epsilon-related transcripts that appeared to be highly relevant to the biological actions of IFN-alpha.
蛋白激酶在人α干扰素(IFN-α)诱导多种人细胞系中特定基因表达和生物活性的过程中发挥关键作用。我们现在报告,添加IFN-α后24小时和48小时,IFN-α增加了蛋白激酶C(PKC-ε)ε亚型的7 kb转录本以及PKC-ε的细胞含量(分别增加了2倍和6倍)。此外,IFN-α显著诱导了一个4.7 kb的转录本,该转录本与PKC-ε特异性而非PKC-η特异性的cDNA探针杂交。IFN-α对4.7 kb PKC-ε相关mRNA的诱导具有以下已报道的经典IFN-α刺激基因的特性:诱导动力学迅速,在IFN-α敏感但非IFN-α抗性细胞系中维持高水平,蛋白合成非依赖性诱导,以及对蛋白酪氨酸激酶活性抑制剂高度敏感。这些结果表明,IFN-α对基因表达的调控不仅包括经典的IFN-α刺激基因,还包括两个与PKC-ε相关转录本的协同调控,这两个转录本似乎与IFN-α的生物学作用高度相关。