AMP-Kinase is a master sensor for cellular energy status. It is activated by high AMP/ATP levels and initiates changes in cellular energy utilization to compensate for low energy status such as increasing fatty acid oxidation, glucose uptake, and insulin sensitivity. Its activation is believed to be beneficial for patients with type II diabetes. The kinase exists as a heterotrimeric complex composed of an alpha-catalytic, gamma-AMP-binding, and beta-scaffolding subunits. The beta-subunit also contains a glycogen binding domain whose physiological relevance is not known. Preliminary data presented here indicates that the beta-subunit does not perform a scaffolding role in mammalian AMPK necessitating the re-evaluation of its model of assembly. A new model of assembly where beta binds to alpha which then binds gamma will be examined by FPLC analysis and co-immunoprecipitation studies using cellular lysates that express various mutants of each subunit. In addition, beta-subunit function will be further tested in vivo by creating betal- subunit mutant mice to address heterotrimer formation through deletion of its C-terminus, and by knock-in of a glycogen binding point mutation to determine the physiological significance of glycogen binding.
| Wong, Kelly A; Lodish, Harvey F (2006) A revised model for AMP-activated protein kinase structure: The alpha-subunit binds to both the beta- and gamma-subunits although there is no direct binding between the beta- and gamma-subunits. J Biol Chem 281:36434-42 |
