Identification of a novel AMP-activated protein kinase β 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 (alpha 2). Using this approach, we have isolated a novel AMPK beta isoform, which we designate AMPK beta 2. The N-terminal region of beta 2 differs significantly from that of the previously characterized isoform (beta 1), suggesting that this region could play a role in isoform-specific AMPK activity. Comparison of the C-terminal sequences of beta 1 and beta 2 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 beta 1 and beta 2 was examined in a number of tissues, revealing that the beta 1 isoform is highly expressed in liver with low expression 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 upstream signaling and/or downstream targeting of the AMPK complex.