MULTIPLE AND COOPERATIVE PHOSPHORYLATION EVENTS REGULATE THE CREM ACTIVATOR FUNCTION
MULTIPLE AND COOPERATIVE PHOSPHORYLATION EVENTS REGULATE THE CREM ACTIVATOR FUNCTION
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DOI：
10.1002/j.1460-2075.1993.tb06068.x
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发表时间：
1993-10-01
期刊：
影响因子：
11.4
通讯作者：
SASSONECORSI, P
中科院分区：
文献类型：
--
作者：
DEGROOT, RP;DENHERTOG, J;SASSONECORSI, P
磷酸化是调节转录因子活性的主要机制之一。我们研究了磷酸化在转录因子 CREM 调节中的作用。我们发现 CREMtau 激活剂在体内多个丝氨酸和苏氨酸残基上被磷酸化。毛喉素、TPA 或 Ca2+ 离子载体对各种信号转导途径的刺激导致丝氨酸 117 磷酸化增强，同时 CREMtau 反式激活潜力增加。我们已经鉴定出多种激酶也可以在体外磷酸化 S117。此外，我们发现酪蛋白激酶 I 和 II 在多个残基上协同磷酸化 CREMtau，从而增强 DNA 结合。还观察到与其他激酶的协同磷酸化。这些结果表明，CREMtau 的活性受到多个磷酸化事件的调节，表明 CREM 可以被视为信号通路可能会聚和/或串扰的核效应器。
Phosphorylation is one of the major mechanisms by which the activity of transcription factors can be regulated. We have investigated the role of phosphorylation in the regulation of the transcription factor CREM. We show that the CREMtau activator is phosphorylated on multiple serine and threonine residues in vivo. Stimulation of various signal transduction pathways by forskolin, TPA or Ca2+ ionophore leads to enhanced phosphorylation of serine 117, concomitant with an increase in the transactivation potential of CREMtau. We have identified multiple kinases that can also phosphorylate S117 in vitro. Moreover, we show that casein kinase I and II cooperatively phosphorylate CREMtau on multiple residues, eliciting enhanced DNA binding. Cooperative phosphorylation is also observed with other kinases. These results show that the activity of CREMtau is regulated by multiple phosphorylation events, suggesting that CREM could be considered as a nuclear effector where signalling pathways may converge and/or cross-talk.