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. Author manuscript; available in PMC: 2012 Mar 2.
Published in final edited form as: Nat Cell Biol. 2011 Sep 2;13(9):1016–1023. doi: 10.1038/ncb2329

Figure 1. The AMPK signaling pathway.

Figure 1

AMPK is activated when AMP and ADP levels in the cells rise due to variety of physiological stresses, as well as pharmacological inducers. LKB1 is the upstream kinase activating it in response to AMP increase, whereas CAMKK2 activates AMPK in response to calcium increase. Activated AMPK directly phosphorylates a number of subtrates to acutely impact metabolism and growth, as well as phosphorylating a number of transcriptional regulators that mediate long term metabolic reprogramming. Shown are all the best-established substrates to date-those needing further in vivo examination are italicized. Question marks denote candidate substrates whose identified phosphorylation sites diverge from the established optimal substrate motif (which all the others conform to). A full lineup of the identified AMPK phosphorylation sites in these substrates in Supplemental Table 1. Substrates in red have been reported to serve as substrates of other AMPK family members (SIK1, SIK2, MARKs, SADs) in vivo in addition to being substrates of AMPK.