CONSTITUTIVE PHOSPHORYLATION OF I-KAPPA-B-ALPHA BY CASEIN KINASE-II
CONSTITUTIVE PHOSPHORYLATION OF I-KAPPA-B-ALPHA BY CASEIN KINASE-II
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DOI：
10.1073/pnas.92.17.7637
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发表时间：
1995-08-15
影响因子：
11.1
通讯作者：
VERMA, IM
中科院分区：
文献类型：
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作者：
BARROGA, CF;STEVENSON, JK;VERMA, IM
核因子-kappa B/Rel蛋白与I kappa Bα的磷酸化形式结合在细胞质中。在多种诱导剂的诱导下，核转录因子-kappa B/Rel蛋白的活性先于I-kappa Bα蛋白的快速降解。我们报道了从未经刺激或刺激的小鼠细胞中鉴定和部分纯化的一种细胞激酶，它特异性地磷酸化I kappa Bα的C末端。酪蛋白激酶II(CKII)在Ikappa Bα的C-末端区域有几个共识的位点。此外，针对CKIIα亚基的抗体可阻断细胞激活酶的活性。如果5个可能被CKII磷酸化的丝氨酸和苏氨酸残基突变为丙氨酸，则不能检测到I kappa BαC末端区域的磷酸化。未经刺激的细胞中的I kappa Bα的二维胰酶磷酸肽图与部分纯化的细胞激酶体外磷酸化I kappa Bα获得的图谱相同。我们认为Ikappa Bα的组成性磷酸化是由CKII完成的。
The NF-kappa B/Rel proteins are sequestered in the cytoplasm in association with the phosphorylated form of I kappa B alpha. Upon induction with a wide variety of agents, the activity of NF-kappa B/Rel proteins is preceded by the rapid degradation of I kappa B alpha protein. We report the identification and partial purification of a cellular kinase from unstimulated or stimulated murine cells, which specifically phosphorylates the C terminus of I kappa B alpha. There are several consensus sites for casein kinase II (CKII) in the C-terminal region of I kappa B alpha. Additionally, the activity of the cellular kinase is blocked by antibodies against the alpha subunit of CKII. No phosphorylation of the C-terminal region of I kappa B alpha can be detected if the five possible serine and threonine residues that can be phosphorylated by CKII are mutated to alanine. A two dimensional tryptic phosphopeptide map of I kappa B alpha from unstimulated cells was identical to that obtained by in vitro phosphorylation of I kappa B alpha with the partially purified cellular kinase. We propose that constitutive phosphorylation of I kappa B alpha is carried out by CKII.