An activating mutation in the γ1 subunit of the AMP-activated protein kinase
An activating mutation in the γ1 subunit of the AMP-activated protein kinase
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DOI：
10.1016/s0014-5793(01)02602-3
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发表时间：
2001-07-06
期刊：
影响因子：
3.5
通讯作者：
Witters, LA
中科院分区：
文献类型：
--
作者：
Hamilton, SR;Stapleton, D;Witters, LA
AMP活化蛋白激酶（AMPK）是一种异源三聚体蛋白，由一个催化性α亚基和两个调节性β和γ亚基组成。γ亚基通过与α亚基的C-末端结合而对酶活性至关重要，并且似乎在确定AMP敏感性方面起一定作用。我们证明，γ 1 R70 Q突变导致AMPK活性显著增加，并使其在很大程度上不依赖AMP。这种激活与α亚基激活环T172的磷酸化增加有关。AMPK的这些体外特征也反映在其主要底物之一乙酰辅酶A羧化酶的细胞内磷酸化增加中。这些数据说明了yl亚基在AMPK调节中的重要性以及AMP对其的调节。(C)2001年欧洲生物化学学会联合会。由Elsevier Science B. V.出版，版权所有。
The AMP-activated protein kinase (AMPK) is a heterotrimeric protein composed of a catalytic a subunit and two regulatory subunits, beta and gamma, The gamma subunit is essential for enzyme activity by virtue of its binding to the C-terminus of the a subunit and appears to play some role in the determination of AMP sensitivity. We demonstrate that a gamma 1R70Q mutation causes a marked increase in AMPK activity and renders it largely AMP-independent, This activation is associated with increased phosphorylation of the a subunit activation loop T172, These in vitro characteristics of AMPK are also reflected in increased intracellular phosphorylation of one of its major substrates, acetyl-CoA carboxylase. These data illustrate the importance of the yl subunit in the regulation of AMPK and its modulation by AMP. (C) 2001 Federation of European Biochemical Societies. Published by Elsevier Science B.V. All rights reserved.