Identification of a novel AMP-activated protein kinase beta subunit isoform that is highly expressed in skeletal muscle.
The AMP-activated protein kinase (AMPK) is a member of a growing family of related kinases, including the SNF1 complex in yeast, which respond to nutritional stress. AMPK is a heterotrimeric complex of a catalytic subunit (alpha) and two regulatory subunits (beta and gamma), and proteins related to all three subunits have been identified in the SNF1 complex. We have used the two-hybrid system in order to identify proteins interacting with the catalytic subunit (alpha2). Using this approach, we have isolated a novel AMPKbeta isoform, which we designate AMPKbeta2. The N-terminal region of beta2 differs significantly from that of the previously characterized isoform (beta1), suggesting that this region could play a role in isoform-specific AMPK activity. Comparison of the C-terminal sequences of beta1 and beta2 with their related proteins in yeast identifies two highly conserved regions predicted to be involved in binding of the alpha and gamma subunits. The expression of beta1 and beta2 was examined in a number of tissues, revealing that the beta1 isoform is highly expressed in liver with low expression in skeletal muscle, whereas the opposite pattern is observed for the beta2 isoform. These results suggest that the beta isoforms have tissue-specific roles, which may involve altered responses to upstream signaling and/or downstream targeting of the AMPK complex.
Thornton
C
C
Medical Research Council Clinical Sciences Centre, Cellular Stress Group, Imperial College School of Medicine, Hammersmith Hospital, DuCane Road, London W12 0NN, United Kingdom.
Snowden
M A
MA
Carling
D
D
D055372:AMP-Activated Protein Kinases; D000595:Amino Acid Sequence; D001483:Base Sequence; D015153:Blotting, Western; D002478:Cells, Cultured; D004591:Electrophoresis, Polyacrylamide Gel; D006801:Humans; D008969:Molecular Sequence Data; D009097:Multienzyme Complexes; D018482:Muscle, Skeletal / Q000201:enzymology*; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases; D017386:Sequence Homology, Amino Acid
D009097:Multienzyme Complexes; D011494:Protein Kinases; C526181:PRKAA2 protein, human; C526182:PRKAB1 protein, human; C526183:PRKAB2 protein, human; D017346:Protein Serine-Threonine Kinases; D055372:AMP-Activated Protein Kinases