CAMKK2

General Information

Full gene name:calcium/calmodulin-dependent protein kinase kinase 2, beta
Entrez Gene ID:10645
Location:12q24.2
Synonyms:CAMKKB, CAMKK
Type:protein-coding

User SNPs

SNPs given by the user that are near or inside this gene:

SNP Distance (bp) Direction
rs7957197 214809 downstream

NCBI Summary

The product of this gene belongs to the Serine/Threonine protein kinase family, and to the Ca(2+)/calmodulin-dependent protein kinase subfamily. The major isoform of this gene plays a role in the calcium/calmodulin-dependent (CaM) kinase cascade by phosphorylating the downstream kinases CaMK1 and CaMK4. Protein products of this gene also phosphorylate AMP-activated protein kinase (AMPK). This gene has its strongest expression in the brain and influences signalling cascades involved with learning and memory, neuronal differentiation and migration, neurite outgrowth, and synapse formation. Alternative splicing results in multiple transcript variants encoding distinct isoforms. The identified isoforms differ in their ability to undergo autophosphorylation and to phosphorylate downstream kinases. [provided by RefSeq, Jul 2012]

OMIM

No OMIM data available for this gene.

NCBI Phenotypes

No phenotypes found linked to this gene.

Gene Ontology

  • calcium ion binding
  • calmodulin-dependent protein kinase activity
  • protein phosphorylation
  • regulation of protein kinase activity
  • MAPK cascade
  • positive regulation of transcription, DNA-dependent
  • protein tyrosine kinase activity
  • calmodulin binding
  • ATP binding
  • cytoplasm
  • intracellular
  • calcium-mediated signaling
  • protein autophosphorylation

GeneRIFs

  • Biochemical Activity [PMID 10187789]
  • Biochemical Activity [PMID 10187789]
  • Data show that protein kinase A (PKA) regulates the alternative splicing of Ca(2)/calmodulin-dependent protein kinase kinase 2 (CaMKK2) to produce variants that differentially modulate neuronal differentiation. [PMID 21957496]
  • Endothelial cells possess two pathways to activate AMPK, one Ca2+/CaMKKbeta dependent and one AMP/LKB1 dependent. [PMID 16880506]
  • Clinical trial of gene-disease association and gene-environment interaction. (HuGE Navigator) [PMID 20379614]
  • Affinity Capture-Western [PMID 12628440]
  • Reconstituted Complex [PMID 19953087]
  • Affinity Capture-MS [PMID 20562859]
  • Affinity Capture-MS [PMID 20562859]
  • Affinity Capture-MS [PMID 20562859]
  • Affinity Capture-MS [PMID 20562859]
  • Affinity Capture-MS [PMID 20562859]
  • Affinity Capture-MS [PMID 20562859]
  • Affinity Capture-MS [PMID 20562859]
  • Affinity Capture-MS [PMID 20562859]
  • Affinity Capture-MS [PMID 20562859]
  • Affinity Capture-MS [PMID 20562859]
  • Affinity Capture-MS [PMID 20562859]
  • Affinity Capture-MS [PMID 20562859]
  • Affinity Capture-MS [PMID 20562859]
  • Affinity Capture-MS [PMID 20562859]
  • Affinity Capture-MS [PMID 20562859]
  • Affinity Capture-MS [PMID 20562859]
  • Affinity Capture-MS [PMID 20562859]
  • Affinity Capture-MS [PMID 20562859]
  • Overexpression of CaMKKbeta in mammalian cells increases AMPK activity, whereas pharmacological inhibition of CaMKK, or downregulation of CaMKKbeta using RNA interference, almost completely abolishes AMPK activation [PMID 16054096]
  • modulating basal AMPK and CAMKKB activity in the hypothalamus is essential for maintaining tight regulation of pathways contributing to food intake [PMID 18436530]
  • Data show that that the prototypical CaM target sequence skMLCK, a fragment from skeletal muscle myosin light chain kinase, binds to CaM in a highly cooperative way, while only a lower degree of interdomain binding cooperativity emerges for CaMKK. [PMID 19667195]
  • phosphorylation of CaMKKbeta regulates its half-life. [PMID 21669867]
  • Observational study of gene-disease association. (HuGE Navigator) [PMID 17197037]
  • a prominent association found between severity of panic- and agoraphobia symptoms and an exonic SNP (rs3817190) in the CaMKKb gene and a trend for association with an exonic SNP in P2RX7 (rs1718119) with severity scores in the panic- and agoraphobia scale [PMID 17197037]
  • ERK activation and cell growth require CaM kinases in MCF-7 breast cancer cells [PMID 19763792]
  • Findings reveal that hypoxia can trigger AMPK activation in the apparent absence of increased [AMP] through ROS-dependent CRAC channel activation, leading to increases in cytosolic calcium that activate the AMPK upstream kinase CaMKKbeta. [PMID 21670147]
  • Our results demonstrate that CaMKKbeta and AMP-activated protein kinase form a unique signaling complex [PMID 21807092]
  • Affinity Capture-MS [PMID 21906983]
  • CaMKK is involved in both S1P receptor- and SR-BI-mediated phosphorylation of AMPK, Akt, and eNOS. [PMID 20018878]
  • Calmodulin-dependent protein kinase kinase-beta activates AMPK without forming a stable complex. There is a synergistic effects of Ca2+ and AMP. [PMID 19958286]
  • Growth of cervical cancer cells was inhibited through activation of CAMKK2 and LBK1. [PMID 19407487]
  • Two-hybrid [PMID 17043677]
  • There is a significant basal activity and phosphorylation of AMPK in LKB1-deficient cells that can be stimulated by Ca2+ ionophores, and studies using the CaMKK inhibitor STO-609 and isoform-specific siRNAs show that CaMKKbeta is required for this effect [PMID 16054095]
  • These results suggest that CaMKK is an important factor for human cytomegalovirus replication and human cytomegalovirus-mediated glycolytic activation. [PMID 21084482]

PubMed Articles

Recent articles:

  • Green MF et al. “Characterization of the CaMKKβ-AMPK signaling complex.” Cell Signal. 2011 Dec;23(12):2005-12. PMID 21807092
  • Cao W et al. “Differential effects of PKA-controlled CaMKK2 variants on neuronal differentiation.” RNA Biol. 2011 Nov-Dec;8(6):1061-72. PMID 21957496
  • Kim W et al. “Systematic and quantitative assessment of the ubiquitin-modified proteome.” Mol Cell. 2011 Oct 21;44(2):325-40. PMID 21906983
  • Wagner SA et al. “A proteome-wide, quantitative survey of in vivo ubiquitylation sites reveals widespread regulatory roles.” Mol Cell Proteomics. 2011 Oct;10(10):M111.013284. PMID 21890473
  • Mungai PT et al. “Hypoxia triggers AMPK activation through reactive oxygen species-mediated activation of calcium release-activated calcium channels.” Mol Cell Biol. 2011 Sep;31(17):3531-45. PMID 21670147
  • Green MF et al. “Ca2+/Calmodulin-dependent protein kinase kinase beta is regulated by multisite phosphorylation.” J Biol Chem. 2011 Aug 12;286(32):28066-79. PMID 21669867
  • McArdle J et al. “Inhibition of calmodulin-dependent kinase kinase blocks human cytomegalovirus-induced glycolytic activation and severely attenuates production of viral progeny.” J Virol. 2011 Jan;85(2):705-14. PMID 21084482
  • Behrends C et al. “Network organization of the human autophagy system.” Nature. 2010 Jul 1;466(7302):68-76. PMID 20562859
  • Rose JE et al. “Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score.” Mol Med. 2010 Jul-Aug;16(7-8):247-53. PMID 20379614
  • Kimura T et al. “Mechanism and role of high density lipoprotein-induced activation of AMP-activated protein kinase in endothelial cells.” J Biol Chem. 2010 Feb 12;285(7):4387-97. PMID 20018878

Top Pubmed articles linked to gene CAMKK2 matching any search term:

  • Racioppi L et al. “Calcium/Calmodulin-dependent Protein Kinase Kinase 2 Regulates Macrophage-mediated Inflammatory Responses.” J Biol Chem. 2012 Mar 30;287(14):11579-91. PMID 22334678
  • Anderson KA et al. “Deletion of CaMKK2 from the liver lowers blood glucose and improves whole-body glucose tolerance in the mouse.” Mol Endocrinol. 2012 Feb;26(2):281-91. PMID 22240810
  • Beck A et al. “An siRNA screen identifies transmembrane 7 superfamily member 3 (TM7SF3), a seven transmembrane orphan receptor, as an inhibitor of cytokine-induced death of pancreatic beta cells.” Diabetologia. 2011 Nov;54(11):2845-55. PMID 21853325
  • Chikahisa S et al. “Central AMPK contributes to sleep homeostasis in mice.” Neuropharmacology. 2009 Sep;57(4):369-74. PMID 19615388
  • Anderson KA et al. “Hypothalamic CaMKK2 contributes to the regulation of energy balance.” Cell Metab. 2008 May;7(5):377-88. PMID 18460329
  • Imai S et al. “Increased intracellular calcium activates serum and glucocorticoid-inducible kinase 1 (SGK1) through a calmodulin-calcium calmodulin dependent kinase kinase pathway in Chinese hamster ovary cells.” Life Sci. 2003 Apr 4;72(20):2199-209. PMID 12628440

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