CKIα is associated with and phosphorylates Star-PAP and is also required for expression of select Star-PAP target messenger RNAs
CKIα is associated with and phosphorylates Star-PAP and is also required for expression of select Star-PAP target messenger RNAs
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DOI：
10.1074/jbc.m800656200
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发表时间：
2008-05-02
影响因子：
4.8
通讯作者：
Anderson, Richard A.
中科院分区：
文献类型：
--
作者：
Gonzales, Michael L.;Mellman, David L.;Anderson, Richard A.
我们最近发现了Star-PAP，这是一种与磷脂酰肌醇-4-磷酸5-激酶Iα(PIPKIα)相关的核多聚(A)聚合酶，是表达特定mRNAs所必需的。StAR-PAP活性直接受PIPKIα产物磷脂酰肌醇4，5-二磷酸(PI-4，5-P-2)的调节，将核磷脂酰肌醇信号与基因表达联系起来。在这里，我们证明了PI-4，5-P-2依赖的蛋白激酶活性也是Star-PAP蛋白复合体的一部分。我们确定PI-4，5-P-2敏感的酪蛋白激酶Iα(CKIα)是负责这种活性的蛋白激酶，并进一步证明CKIα能够直接磷酸化Star-PAP。CKIα和PIPKIα都是合成某些而不是全部Star-PAP靶基因所必需的，并且像Star-PAP一样，CKIα在体内与这些信息有关。综上所述，这些数据表明CKIα、PIPKIα和Star-PAP共同调节特定Star-PAP消息的产生。因此，Star-PAP复合体代表了一个多条信号通路汇聚的位置，以调节特定mRNAs的表达。
We have recently identified Star-PAP, a nuclear poly( A) polymerase that associates with phosphatidylinositol-4-phosphate 5-kinase I alpha (PIPKI alpha) and is required for the expression of a specific subset of mRNAs. Star-PAP activity is directly modulated by the PIPKI alpha product phosphatidylinositol 4,5-bisphosphate (PI-4,5-P-2), linking nuclear phosphoinositide signaling to gene expression. Here, we show that PI-4,5-P-2-dependent protein kinase activity is also a part of the Star-PAP protein complex. We identify the PI-4,5- P-2-sensitive casein kinase I alpha (CKI alpha) as a protein kinase responsible for this activity and further show that CKI alpha is capable of directly phosphorylating Star-PAP. Both CKI alpha and PIPKI alpha are required for the synthesis of some but not all Star-PAP target mRNA, and like Star-PAP, CKI alpha is associated with these messages in vivo. Taken together, these data indicate that CKI alpha, PIPKI alpha, and Star-PAP function together to modulate the production of specific Star-PAP messages. The Star-PAP complex therefore represents a location where multiple signaling pathways converge to regulate the expression of specific mRNAs.