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Assaying Protein Kinase Activity with Radiolabeled ATP
Published on: May 26, 2017
TAK1是MKK和IKK的依赖于全方位素的酶
1Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, Texas 75390-9148, USA.
Nature
|July 19, 2001
概括
瘤亡因子受体相关因子6 (TRAF6) 激活关键的炎症激酶. 这项研究确定了TRIKA2,TAK1复合体,揭示了无处不在.
科学领域:
- * 分子和细胞生物学
- * 免疫学 免疫学
- * * 信号转导 信号转导
背景情况:
- *瘤亡因子受体相关因子6 (TRAF6) 是一种关键的信号转换器,用于诸如介素-1 (IL-1) 和脂多糖类 (LPS) 等促炎媒介.
- * TRAF6激活IkappaB激酶 (IKK) 和Jun氨基终端激酶 (JNK) 途径,这对于细胞应激反应至关重要.
- *以前的理解表明,TRAF6介导的IKK激活涉及中间因子TRIKA1和TRIKA2,但TRIKA2的组成和机制仍然难以捉摸.
研究的目的:
- * 净化和识别TRIKA2的组件,TRIKA2是TRAF6中介信号传输的关键中间体.
- *阐明TRIKA2对IKK和JNK通路激活的作用机制.
- * 为了研究在调节这些关键的应激反应途径中无处不在的作用.
主要方法:
- * 用蛋白质净化和复杂的识别技术来分离和描述TRIKA2.
- *进行了体外激酶试验,以评估TAK1复合物的酸化活性在IKK和MKK6.
- * 用多比基因化试验检测和分析TRAF6上与Lys 63 (K63) 相关的多比基因链及其对通路激活的影响.
主要成果:
- *TRIKA2被确定为一个由TAK1,TAB1和TAB2组成的复合体.
- *依赖TRAF6和Ubc13-Uev1A的TAK1激酶复合物酸化并激活IKK.
- * Lys 63 (K63) 相关的多基化被证明可以直接调节TAK1对MK6的活性,并被发现与TRAF6.6结合.
结论:
- * 泛化,特别是与K63结合的多聚化,在炎症和压力反应信号通路中起着关键的调节作用.
- * 鉴定TRIKA2为TAK1复合体,提供了TRAF6介导的泛化和IKK和JNK通路的激活之间的机制联系.
- * 这项研究揭示了一种独特的,蛋白质酶独立的,由K63结合的多基因链介导的IKK激活机制,突出了在细胞信号传递中泛化的重要性.
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