How is AMPK activated?

AMPK is activated when ADP and AMP levels in the cell rise due to various physiological stresses. LKB1 is one upstream kinase activating AMPK in response to the AMP increase. The enzyme CAMKK2 is another upstream kinase that activates AMPK, but in response to calcium increase. AMPK activation positively regulates signaling pathways that recycle ATP sources, including autophagy and fatty acid oxidation. AMP allosterically stimulates AMPK activity by binding to the gamma subunit, which carries four CBS domains organized into two pairs known as Bateman domains. The phosphorylation of Thr172 within the activation loop is required for maximal activity of AMPK.