p-AMPK heterotrimer AMPK heterotrimer Activation of cytosolic AMPK by phosphorylation Authored: Gopinathrao, G, 2007-07-29 21:03:03 EC Number: 2.7.11 Edited: Jassal, B, 2009-11-20 Pubmed11018120 Pubmed11797013 Pubmed14511394 Pubmed14614828 Pubmed14985505 Pubmed15579580 Pubmed16054041 Pubmed8779952 Reactome Database ID Release 43200421 Reactome, http://www.reactome.org ReactomeREACT_11183 Reviewed: Zheng, B, 2009-10-20 The cytosolic AMPK complex is activated by phosphorylation. LKB1 phosphorylates AMPK heterotrimer on Thr174 of the alpha 1 subunit (or Thr172 on alpha 2 subunit) leading to activation of AMPK (if cellular AMP/ATP ratio is high) (Hawley SA et al, 2003; Woods A et al, 2003; Shaw RJ et al, 2004). Signals leading to this phosphorylation event can be mediated by exercise, leptin and adiponectin, the hypothalamic-sympathetic nervous system (SNS), and alpha adrenergic receptors, as demonstrated in studies of rat and human skeletal muscle (Minoksohi et al, 2002, Kahn et al, 2005). The details of AMPK activation in response to these stimuli will be annotated in the future. Nuclear AMPK may well be a substrate for LKB1 but, to date, there is no clear evidence for this.