Inositol 1,3,4-trisphosphate 5/6-kinase associates with the COP9 signalosome by binding to CSN1
Inositol 1,3,4-trisphosphate 5/6-kinase associates with the COP9 signalosome by binding to CSN1
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DOI：
10.1074/jbc.m208709200
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发表时间：
2002-11-29
影响因子：
4.8
通讯作者：
Majerus, PW
中科院分区：
文献类型：
--
作者：
Sun, Y;Wilson, MP;Majerus, PW
COP9信号体（CSN）是一个由8个蛋白组成的复合体，首次被鉴定为植物光形态发生的抑制因子。与COP9信号体相关的蛋白激酶活性已被报道，但尚未确定；我们提出了肌醇1,3,4-三磷酸5/6激酶（5/6激酶）作为与COP9信号体相关的蛋白激酶的证据。我们已经证明，无论是从牛脑中纯化还是转染到HEK 293细胞中，5/6-激酶都存在于与八组分COP9信号体的复合物中。5/6-激酶磷酸化与COP9信号体相同的底物，包括IkappaBalpha、p53和c-Jun，但不能磷酸化其他几种底物，包括c-Jun 1-79，它们不是COP9相关激酶的底物。COP9信号体相关激酶和5/6激酶均受到姜黄素的抑制。5/6-激酶与COP9信号体的关联是通过与CSN1的相互作用，CSN1与5/6-激酶产生免疫沉淀。此外，5/6-激酶的肌醇激酶活性在与CSN1复合物时受到抑制。我们认为5/6激酶是先前描述的COP9信号体相关激酶。
The COP9 signalosome (CSN) is a complex of eight proteins first identified as a repressor of plant photomorphogenesis. A protein kinase activity associated with the COP9 signalosome has been reported but not identified; we present evidence for inositol 1,3,4-trisphosphate 5/6-kinase (5/6-kinase) as a protein kinase associated with the COP9 signalosome. We have shown that 5/6-kinase exists in a complex with the eight-component COP9 signalosome both when purified from bovine brain and when transfected into HEK 293 cells. 5/6-kinase phosphorylates the same substrates as those of the COP9 signalosome, including IkappaBalpha, p53, and c-Jun but fails to phosphorylate several other substrates, including c-Jun 1-79, which are not substrates for the COP9-associated kinase. Both the COP9 signalosome-associated kinase and 5/6-kinase are inhibited by curcumin. The association of 5/6-kinase with the COP9 signalosome is through an interaction with CSN1, which immunoprecipitates with 5/6-kinase. In addition, the inositol kinase activity of 5/6-kinase is inhibited when in a complex with CSN1. We propose that 5/6-kinase is the previously described COP9 signalosome-associated kinase.