An activating mutation in the gamma1 subunit of the AMP-activated protein kinase.
The AMP-activated protein kinase (AMPK) is a heterotrimeric protein composed of a catalytic alpha 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 alpha subunit and appears to play some role in the determination of AMP sensitivity. We demonstrate that a gamma1R70Q mutation causes a marked increase in AMPK activity and renders it largely AMP-independent. This activation is associated with increased phosphorylation of the alpha 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 gamma1 subunit in the regulation of AMPK and its modulation by AMP.
Hamilton
S R
SR
Endocrine-Metabolism Division, Departments of Medicine and Biochemistry, Dartmouth Medical School, Hanover, NH 03755-3833, USA.
Stapleton
D
D
O'Donnell
J B
JB
Kung
J T
JT
Dalal
S R
SR
Kemp
B E
BE
Witters
L A
LA
D055372:AMP-Activated Protein Kinases; D019943:Amino Acid Substitution; D000818:Animals; D019556:COS Cells; D002352:Carrier Proteins; D002460:Cell Line; D004789:Enzyme Activation / Q000235:genetics; D015870:Gene Expression; D006801:Humans; D007527:Isoenzymes / Q000235:genetics; D016297:Mutagenesis, Site-Directed; D010766:Phosphorylation; D011494:Protein Kinases / Q000235:genetics* / Q000378:metabolism*; D017434:Protein Structure, Tertiary / Q000235:genetics; D021122:Protein Subunits; D029701:Saccharomyces cerevisiae Proteins; D016415:Sequence Alignment; D013329:Structure-Activity Relationship; D014157:Transcription Factors / Q000235:genetics; D014162:Transfection; D015003:Yeasts
D002352:Carrier Proteins; D007527:Isoenzymes; D021122:Protein Subunits; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; D011494:Protein Kinases; C526222:PRKAG1 protein, human; C078651:SNF4 protein, S cerevisiae; D055372:AMP-Activated Protein Kinases