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 famil y of related kinases, including the SNF1 complex in yeast, which respo nd to nutritional stress. AMPK is a heterotrimeric complex of a cataly tic subunit (alpha) and two regulatory subunits (beta and gamma), and proteins related to all three subunits have been identified in the SNF 1 complex. We have used the two-hybrid system in order to identify pro teins interacting with the catalytic subunit (alpha 2). Using this app roach, we have isolated a novel AMPK beta isoform, which we designate AMPK beta 2. The N-terminal region of beta 2 differs significantly fro m that of the previously characterized isoform (beta 1), suggesting th at this region could play a role in isoform-specific AMPK activity. Co mparison of the C-terminal sequences of beta 1 and beta 2 with their r elated proteins in yeast identifies two highly conserved regions predi cted to be involved in binding of the alpha and gamma subunits. The ex pression of beta 1 and beta 2 was examined in a number of tissues, rev ealing that the beta 1 isoform is highly expressed in liver with low e xpression in skeletal muscle, whereas the opposite pattern is observed for the beta 2 isoform. These results suggest that the beta isoforms have tissue-specific roles, which may involve altered responses to ups tream signaling and/or downstream targeting of the AMPK complex.