An activating mutation in the gamma 1 subunit of the AMP-activated proteinkinase

The AMP-activated protein kinase (AMPK) is a heterotrimeric protein compose d 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 deter mination of AMP sensitivity. We demonstrate that a gamma 1R70Q mutation cau ses a marked increase in AMPK activity and renders it largely AMP-independe nt, This activation is associated with increased phosphorylation of the a s ubunit activation loop T172, These in vitro characteristics of AMPK are als o 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) 20 01 Federation of European Biochemical Societies. Published by Elsevier Scie nce B.V. All rights reserved.