Figure 1. Canonical mechanism of activation of AMPK by adenine nucleotides, and the Ca2+-dependent mechanism mediated by CaMKKβ.
AMP binding activates AMPK by three effects, i.e. promotion of Thr172 phosphorylation by LKB1 (effect #1), inhibition of Thr172 dephosphorylation by protein phosphatases (PP) (effect #2), and allosteric activation (effect #3). All three effects are opposed by binding of ATP, while binding of ADP mimics effect #2 and #1, but not #3. CaMKKβ phosphorylates the same site as LKB1 (Thr172) in response to increases in cellular Ca2+.