AMP-activated protein kinase-mediated feedback phosphorylation controls the Ca/calmodulin (CaM) dependence of Ca/CaM-dependent protein kinase kinase β.

The Ca/calmodulin-dependent protein kinase kinase β (CaMKKβ)/5'-AMP-activated protein kinase (AMPK) phosphorylation cascade affects various Ca-dependent metabolic pathways and cancer growth. Unlike recombinant CaMKKβ that exhibits higher basal activity (autonomous activity), activation of the CaMKKβ/AMPK signaling pathway requires increased intracellular Ca concentrations. Moreover, the Ca/CaM dependence of CaMKKβ appears to arise from multiple phosphorylation events, including autophosphorylation and activities furnished by other protein kinases.