Publication Date
11-18-2024
Journal
Essays in Biochemistry
DOI
10.1042/EBC20240011
PMID
39268917
PMCID
PMC11576191
PubMedCentral® Full Text Version
Post-Print
Published Open-Access
yes
Keywords
Calcium-Calmodulin-Dependent Protein Kinase Kinase, Humans, Calcium Signaling, Energy Metabolism, Animals, Calcium, Neoplasms, AMP-Activated Protein Kinases, AMPK, calcium signaling, calmodulin, CaMKK2, energy-sensing
Abstract
Calcium (Ca2+) ions are ubiquitous and indispensable signaling messengers that regulate virtually every cell function. The unique ability of Ca2+ to regulate so many different processes yet cause stimulus specific changes in cell function requires sensing and decoding of Ca2+ signals. Ca2+-sensing proteins, such as calmodulin, decode Ca2+ signals by binding and modifying the function of a diverse range of effector proteins. These effectors include the Ca2+-calmodulin dependent protein kinase kinase-2 (CaMKK2) enzyme, which is the core component of a signaling cascade that plays a key role in important physiological and pathophysiological processes, including brain function and cancer. In addition to its role as a Ca2+ signal decoder, CaMKK2 also serves as an important junction point that connects Ca2+ signaling with energy metabolism. By activating the metabolic regulator AMP-activated protein kinase (AMPK), CaMKK2 integrates Ca2+ signals with cellular energy status, enabling the synchronization of cellular activities regulated by Ca2+ with energy availability. Here, we review the structure, regulation, and function of CaMKK2 and discuss its potential as a treatment target for neurological disorders, metabolic disease, and cancer.
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Biological Phenomena, Cell Phenomena, and Immunity Commons, Life Sciences Commons, Medical Cell Biology Commons, Medical Microbiology Commons, Medical Molecular Biology Commons, Medical Specialties Commons
