AMP-activated protein kinase-mediated feedback phosphorylation controls the Ca²⁺/calmodulin (CaM) dependence of Ca²⁺/CaM-dependent protein kinase kinase β.

ABSTRACT: The Ca²⁺/calmodulin-dependent protein kinase kinase β (CaMKKβ)/5'-AMP-activated protein kinase (AMPK) phosphorylation cascade affects various Ca²⁺-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 Ca²⁺ concentrations. Moreover, the Ca²⁺/CaM dependence of CaMKKβ appears to arise from multiple phosphorylation events, including autophosphorylation and activities furnished by other protein kinases. However, the effects of proximal downstream kinases on CaMKKβ activity have not yet been evaluated. Here, we demonstrate feedback phosphorylation of CaMKKβ at multiple residues by CaMKKβ-activat

SUBMITTER: Nakanishi A 

PROVIDER: S-EPMC5712620 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature