Di Maira G, Salvi M, Arrigoni G, Marin O, Sarno S, Brustolon F, Pinna L A, Ruzzene M
Venetian Institute of Molecular Medicine (VIMM), University of Padova, Padova, Italy.
Cell Death Differ. 2005 Jun;12(6):668-77. doi: 10.1038/sj.cdd.4401604.
Treatment of Jurkat cells with specific inhibitors of protein kinase CK2 induces apoptosis. Here we provide evidence that the anti-apoptotic effect of CK2 can be at least partially mediated by upregulation of the Akt/PKB pathway. Such a conclusion is based on the following observations: (1) inhibition of CK2 by cell treatment with two structurally unrelated CK2 inhibitors induces downregulation of Akt/PKB, as judged from decreased phosphorylation of its physiological targets, and immunoprecipitate kinase assay; (2) similar results are observed upon reduction of CK2 catalytic subunit by the RNA-interference technique; (3) Akt/PKB Ser129 is phosphorylated by CK2 in vitro and in vivo; (4) such a phosphorylation of activated Akt/PKB correlates with a further increase in catalytic activity. These data disclose an unanticipated mechanism by which constitutive phosphorylation by CK2 may be required for maximal activation of Akt/PKB.
用蛋白激酶CK2的特异性抑制剂处理Jurkat细胞可诱导细胞凋亡。在此我们提供证据表明，CK2的抗凋亡作用至少部分可通过上调Akt/PKB信号通路来介导。这一结论基于以下观察结果：（1）用两种结构不相关的CK2抑制剂处理细胞抑制CK2后，Akt/PKB会下调，这可从其生理靶点磷酸化水平降低以及免疫沉淀激酶分析判断得出；（2）通过RNA干扰技术降低CK2催化亚基后也观察到类似结果；（3）Akt/PKB的Ser129在体外和体内均可被CK2磷酸化；（4）活化的Akt/PKB的这种磷酸化与催化活性的进一步增加相关。这些数据揭示了一种意想不到的机制，即CK2的组成性磷酸化可能是Akt/PKB最大程度激活所必需的。
