The AMP-activated protein kinase (AMPK) is an αβγ heterotrimer and is regarded as a master metabolic regulator critical to cellular energy homeostasis. The metabolic dimensions of diseases including type 2 diabetes, obesity, cardiovascular disease and cancer, have encouraged efforts to develop direct activating drugs for AMPK.

AMPK signalling involves the phosphorylation of Thr172 on the activation loop of the AMPK α subunit by upstream kinases. We have shown that AMPK phosphorylated at β1-S108 is sensitive to activation by the compound A-769662 independently of Thr172 phosphorylation. In addition, several kinases have been identified as being able to phosphorylate this site in vitro and under specific cellular conditions. These results suggest new possibilities for AMPK regulation in the cell, and have important implications for AMPK-targeted therapeutics.