title: AMPK is a direct adenylate charge-regulated protein kinase.
abstract: The adenosine monophosphate (AMP)-activated protein kinase (AMPK) regulates whole-body and cellular energy balance in response to energy demand and supply. AMPK is an αβγ heterotrimer activated by decreasing concentrations of adenosine triphosphate (ATP) and increasing AMP concentrations. AMPK activation depends on phosphorylation of the α catalytic subunit on threonine-172 (Thr(172)) by kinases LKB1 or CaMKKβ, and this is promoted by AMP binding to the γ subunit. AMP sustains activity by inhibiting dephosphorylation of α-Thr(172), whereas ATP promotes dephosphorylation. Adenosine diphosphate (ADP), like AMP, bound to γ sites 1 and 3 and stimulated α-Thr(172) phosphorylation. However, in contrast to AMP, ADP did not directly activate phosphorylated AMPK. In this way, both ADP/ATP and AMP/ATP ratios contribute to AMPK regulation.
authors.affiliation: Department of Protein Chemistry and Metabolism, St. Vincent's Institute of Medical Research, University of Melbourne, 41 Victoria Parade, Fitzroy 3065, Victoria, Australia. joakhill@svi.edu.au
authors.forename: Jonathan S
authors.initials: JS
authors.lastname: Oakhill
authors.forename: Rohan
authors.initials: R
authors.lastname: Steel
authors.forename: Zhi-Ping
authors.initials: ZP
authors.lastname: Chen
authors.forename: John W
authors.initials: JW
authors.lastname: Scott
authors.forename: Naomi
authors.initials: N
authors.lastname: Ling
authors.forename: Shanna
authors.initials: S
authors.lastname: Tam
authors.forename: Bruce E
authors.initials: BE
authors.lastname: Kemp
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000737:chemistry / Q000378:metabolism*; D000244:Adenosine Diphosphate / Q000378:metabolism*; D000249:Adenosine Monophosphate / Q000378:metabolism*; D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D001665:Binding Sites; D019556:COS Cells; D054737:Calcium-Calmodulin-Dependent Protein Kinase Kinase / Q000378:metabolism; D002522:Chlorocebus aethiops; D004789:Enzyme Activation; D019814:Myristic Acid / Q000378:metabolism; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D021122:Protein Subunits / Q000737:chemistry / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D013912:Threonine / Q000378:metabolism
chemical_list: D021122:Protein Subunits; D011993:Recombinant Fusion Proteins; D019814:Myristic Acid; D013912:Threonine; D000249:Adenosine Monophosphate; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D017346:Protein Serine-Threonine Kinases; D054737:Calcium-Calmodulin-Dependent Protein Kinase Kinase; D055372:AMP-Activated Protein Kinases