Historical Background
CaMKK2 was originally purified and characterized from rat brain as a CaMKI-activating kinase by Edelman et al. (1996). These authors demonstrated that CaMKK2 activated CaMKI and CaMKIV by phosphorylating an equivalent Thr residue within the “activation loop” region of both proteins. Later, rat and human CaMKK2 were cloned and characterized by two independent groups, which provided substantial information about the structure and function of CaMKK2 (Anderson et al. 1998; Kitani et al. 1997). The cAMP-activated protein kinase (AMPK) was subsequently identified as an additional substrate of CaMKK2 in 2005 (Hawley et al. 2005; Woods et al. 2005). The discovery of AMPK as a downstream target of CaMKK2 was an important milestone, which opened new research perspectives, providing mechanistic evidence for studying...
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Anderson KA, et al. Components of a calmodulin-dependent protein kinase cascade. Molecular cloning, functional characterization and cellular localization of Ca2+/calmodulin-dependent protein kinase kinase beta. J Biol Chem. 1998;273:31880–9.
Anderson KA, et al. Hypothalamic CaMKK2 contributes to the regulation of energy balance. Cell Metab. 2008;7:377–88.
Barden N, et al. Analysis of single nucleotide polymorphisms in genes in the chromosome 12Q24.31 region points to P2RX7 as a susceptibility gene to bipolar affective disorder. Am J Med Genet B Neuropsychiatr Genet. 2006;141B:374–82.
Edelman AM, et al. Multiple Ca(2+)-calmodulin-dependent protein kinase kinases from rat brain. Purification, regulation by Ca(2+)-calmodulin, and partial amino acid sequence. J Biol Chem. 1996;271:10806–10.
Hawley SA, et al. Calmodulin-dependent protein kinase kinase-beta is an alternative upstream kinase for AMP-activated protein kinase. Cell Metab. 2005;2:9–19.
Kitani T, Okuno S, Fujisawa H. Molecular cloning of Ca2+/calmodulin-dependent protein kinase kinase beta. J Biochem. 1997;122:243–50.
Luo XJ, et al. Convergent lines of evidence support CAMKK2 as a schizophrenia susceptibility gene. Mol Psychiatry. 2014;19:774–83.
Mairet-Coello G, et al. The CAMKK2-AMPK kinase pathway mediates the synaptotoxic effects of Aβ oligomers through Tau phosphorylation. Neuron. 2013;78:94–108.
Marcelo KL, Means AR, York B. The Ca(2+)/calmodulin/CaMKK2 axis: nature’s metabolic CaMshaft. Trends Endocrinol Metab. 2016;27(10):706–18.
Racioppi L, Means AR. Calcium/calmodulin-dependent protein kinase kinase 2: roles in signaling and pathophysiology. J Biol Chem. 2012;287:31658–65.
Racioppi L, Noeldner PK, Lin F, Arvai S, Means AR. Calcium/calmodulin-dependent protein kinase kinase 2 regulates macrophage-mediated inflammatory responses. J Biol Chem. 2012;287:11579–91.
Scott JW, et al. Autophosphorylation of CaMKK2 generates autonomous activity that is disrupted by a T85S mutation linked to anxiety and bipolar disorder. Sci Rep. 2015;5:14436.
Teng EC, Racioppi L, Means AR. A cell-intrinsic role for CaMKK2 in granulocyte lineage commitment and differentiation. J Leukoc Biol. 2011;90:897–909.
Tokumitsu H, Wayman GA, Muramatsu M, Soderling TR. Calcium/calmodulin-dependent protein kinase kinase: identification of regulatory domains. Biochemistry. 1997;36:12823–7.
Woods A, et al. Ca2+/calmodulin-dependent protein kinase kinase-beta acts upstream of AMP-activated protein kinase in mammalian cells. Cell Metab. 2005;2:21–33.
Acknowledgments
Pilot grant from the Opportunity Funds Management Core of the Centers for Medical Countermeasures against Radiation, National Institute of Allergy and Infectious Diseases; grant number U19AI067773 awarded to L.R
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Huang, W., Racioppi, L. (2018). Calcium Calmodulin Kinase Kinase 2. In: Choi, S. (eds) Encyclopedia of Signaling Molecules. Springer, Cham. https://doi.org/10.1007/978-3-319-67199-4_101573
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DOI: https://doi.org/10.1007/978-3-319-67199-4_101573
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