Protein kinase CK2 phosphorylates and upregulates Akt/PKB
Protein kinase CK2 phosphorylates and upregulates Akt/PKB
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DOI：
10.1038/sj.cdd.4401604
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发表时间：
2005-06-01
影响因子：
12.4
通讯作者：
Ruzzene, M
中科院分区：
文献类型：
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作者：
Di Maira, G;Salvi, M;Ruzzene, M
用蛋白激酶CK 2的特异性抑制剂处理Jurkat细胞诱导凋亡。在这里，我们提供的证据表明，CK 2的抗凋亡作用可以至少部分介导的Akt/PKB途径的上调。这一结论是基于以下观察结果：（1）用两种结构上不相关的CK 2抑制剂处理细胞可诱导Akt/PKB下调，这可从其生理靶点的磷酸化水平降低和免疫沉淀激酶测定来判断：（2）用RNA干扰技术还原CK 2催化亚基时观察到类似的结果;（3）Akt/PKB Ser 129在体外和体内均被CK 2磷酸化，（4）Akt/PKB的这种磷酸化与催化活性的进一步增加相关。这些数据揭示了一个意想不到的机制，CK 2的组成性磷酸化可能需要Akt/PKB的最大激活。
Treatment of Jurkat cells with specific inhibitors of protein kinase CK2 induces apoptosis. Here we provide evidence that the antiapoptotic 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.