An activating mutation in the γ1 subunit of the AMP‐activated protein kinase

FEBS Letters

O'Donnell, John B.²  Hamilton, Stephen R.²  Kemp, Bruce E.¹  Witters, Lee A.²  Dalal, Sushila R.²  Stapleton, David¹  Kung, Jacqueline T.² 

[1]St. Vincent's Institute of Medical Research, St. Vincent's Hospital, 41 Victoria Parade, Fitzroy, Vic. 3065, Australia

[2]Endocrine-Metabolism Division, Departments of Medicine and Biochemistry, Dartmouth Medical School, Remsen 322, Hanover, NH 03755-3833, USA

关键词: Protein kinase;    AMP;    AMP-activated protein kinase;    Cystathionine β-synthase;    Cystathionine β-synthase domain;    ACC;    acetyl-CoA carboxylase;    AICAR;    5-amino-4-imidazolecarboxamide-riboside;    AMPK;    AMP-activated protein kinase;    AMPKK;    AMPK kinase;    CBS;    cystathionine β-synthase;    HA;    hemagglutinin;    NHE;    Na+/H+ exchanger;    PRKAG3;    Hampshire pig AMPK γ3 isoform;   

DOI  :  10.1016/S0014-5793(01)02602-3

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

The AMP-activated protein kinase (AMPK) is a heterotrimeric protein composed of a catalytic α subunit and two regulatory subunits, β and γ. The γ subunit is essential for enzyme activity by virtue of its binding to the C-terminus of the α subunit and appears to play some role in the determination of AMP sensitivity. We demonstrate that a γ1R70Q mutation causes a marked increase in AMPK activity and renders it largely AMP-independent. This activation is associated with increased phosphorylation of the α 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 γ1 subunit in the regulation of AMPK and its modulation by AMP.

【 授权许可】

Unknown