Table 1.

Characteristic features of the upstream kinases of AMPK

Kinase	Physiological function
LKB1	Constitutively switched-on in cells. Under conditions of low cellular energy, i.e., high cellular AMP/ATP ratios, AMP binding causes conformational changes, which allows LKB1 to phosphorylate AMPKα [47].
CaMKK	An alternative AMPK kinase in LKB-1-deficient cell lines, which is activated in response to elevated cytosolic Ca2+ levels [41–43]. Recent evidence suggests that CaMKK-induced AMPK activation plays an important role in Ca2+-regulated glucose and fatty acid metabolism in contracting skeletal muscle [48]. In addition, CaMKK plays a crucial role in T cell antigen receptor-induced rapid activation of AMPK in response to Ca2+ signaling in T lymphocytes [49].
TAK1	An upstream kinase of the MAP-kinase signaling pathway involved in cardiac biology and disease. It was found that inhibition of TAK1 in mice by a cardiac-specific dominant-negative mutation evoked electrophysiological and biochemical properties reminiscent of human Wolff-Parkinson-White syndrome, arising from mutations in AMPK [50]. TAK1 was found to mediate TRAIL-induced autophagy in MCF-10A breast epithelial cells by targeting AMPK phosphorylation [45].
ATM	A major player in response to DNA double-strand breakage. It was reported that ATM phosphorylates AMPKα in etoposide-treated HeLa cells [46]. However, a separate study indicated that ROS-induced ATM activation increased AMPK phosphorylation via an LKB1-dependent mechanism [51].