CAMKK2

Summary

Gene Symbol: CAMKK2
Description: calcium/calmodulin dependent protein kinase kinase 2
Alias: CAMKK, CAMKKB, calcium/calmodulin-dependent protein kinase kinase 2, CAMKK beta protein, caM-KK 2, caM-KK beta, caM-kinase kinase 2, caM-kinase kinase beta, calcium/calmodulin-dependent protein kinase beta, calcium/calmodulin-dependent protein kinase kinase 2, beta
Species: human
Products:     CAMKK2

Top Publications

  1. Mungai P, Waypa G, Jairaman A, Prakriya M, Dokic D, Ball M, et al. Hypoxia triggers AMPK activation through reactive oxygen species-mediated activation of calcium release-activated calcium channels. Mol Cell Biol. 2011;31:3531-45 pubmed publisher
    ..of the AMPK upstream kinase LKB1 by siRNA does not prevent AMPK activation during hypoxia, but knockdown of CaMKK? abolishes the AMPK response...
  2. Anderson K, Means R, Huang Q, Kemp B, Goldstein E, Selbert M, 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 pubmed
    ..The strict Ca2+ requirement of CaMKIV-dependent phosphorylation of cAMP response element-binding protein, is therefore controlled at the level of CaMKIV rather than CaMKK.
  3. Woods A, Dickerson K, Heath R, Hong S, Momcilovic M, Johnstone S, 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 pubmed
    ..Here we show that AMPK is also activated by Ca(2+)/calmodulin-dependent protein kinase kinase (CaMKK)...
  4. Stahmann N, Woods A, Carling D, Heller R. Thrombin activates AMP-activated protein kinase in endothelial cells via a pathway involving Ca2+/calmodulin-dependent protein kinase kinase beta. Mol Cell Biol. 2006;26:5933-45 pubmed
    ..Inhibition of CaMKK with STO-609 or downregulation of CaMKKbeta using RNA interference decreased thrombin-induced AMPK activation ..
  5. Yu S, Chan D, Liu V, Ngan H. Inhibition of cervical cancer cell growth through activation of upstream kinases of AMP-activated protein kinase. Tumour Biol. 2009;30:80-5 pubmed publisher
    ..These data suggest that A23187 could be an alternative potential therapeutic drug used for anti-proliferation in LKB1-deficient cancer cells. ..
  6. Hawley S, Pan D, Mustard K, Ross L, Bain J, Edelman A, et al. Calmodulin-dependent protein kinase kinase-beta is an alternative upstream kinase for AMP-activated protein kinase. Cell Metab. 2005;2:9-19 pubmed
    ..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...
  7. Thornton C, Sardini A, Carling D. Muscarinic receptor activation of AMP-activated protein kinase inhibits orexigenic neuropeptide mRNA expression. J Biol Chem. 2008;283:17116-22 pubmed publisher
    ..These data support a hypothesis that modulating basal AMPK activity in the hypothalamus is essential for maintaining tight regulation of pathways contributing to food intake. ..
  8. Tian S, Ge X, Wu K, Yang H, Liu Y. Ramipril protects the endothelium from high glucose-induced dysfunction through CaMKKβ/AMPK and heme oxygenase-1 activation. J Pharmacol Exp Ther. 2014;350:5-13 pubmed publisher
    ..However, treatment of HAECs with STO-609, a CaMKKβ (Ca(2+)/calmodulin-dependent protein kinase kinase-β) inhibitor; compound C, an AMPK (AMP-activated protein ..
  9. Li Y, Qiao J, Wang B, Bai M, Shen J, Cheng Y. Paeoniflorin Ameliorates Fructose-Induced Insulin Resistance and Hepatic Steatosis by Activating LKB1/AMPK and AKT Pathways. Nutrients. 2018;10: pubmed publisher
    ..of tumor suppressor serine/threonine kinase (LKB)1 but not Ca2+/CaM-dependent protein kinase kinase (CaMKK)β...

More Information

Publications145 found, 100 shown here

  1. Liu Y, Shi D, Tian Y, Liu Y, Zhan Q, Xu J, et al. Eicosapentaenoic Acid-Enriched Phosphatidylcholine Attenuated Hepatic Steatosis Through Regulation of Cholesterol Metabolism in Rats with Nonalcoholic Fatty Liver Disease. Lipids. 2017;52:119-127 pubmed publisher
    ..AMPK) as well as its modulators, liver kinase B1 (LKB1) and Ca2+/calmodulin-dependent kinase kinase (CAMKK)...
  2. Sekar P, Huang D, Hsieh S, Chang S, Lin W. AMPK-dependent and independent actions of P2X7 in regulation of mitochondrial and lysosomal functions in microglia. Cell Commun Signal. 2018;16:83 pubmed publisher
    ..Altogether ROS- and CaMKK-dependent AMPK activation is involved in P2X7-mediated mitophagy, mitochondrial dynamics and lysosomal biogenesis ..
  3. Olianas M, Dedoni S, Onali P. Muscarinic Acetylcholine Receptors Potentiate 5'-Adenosine Monophosphate-Activated Protein Kinase Stimulation and Glucose Uptake Triggered by Thapsigargin-Induced Store-Operated Ca2+ Entry in Human Neuroblastoma Cells. Neurochem Res. 2018;43:245-258 pubmed publisher
    ..molecular component STIM1, or inhibition of Ca2+/calmodulin (CaM)-dependent protein kinase kinase ? (CaMKK?)...
  4. Dou C, Chen Y, Ding N, Li N, Jiang H, Zhao C, et al. Xanthotoxin prevents bone loss in ovariectomized mice through the inhibition of RANKL-induced osteoclastogenesis. Osteoporos Int. 2016;27:2335-2344 pubmed publisher
    ..treatment also suppressed RANKL-induced Ca(2+) oscillations and the activation of the resultant downstream calcium-CaMKK/PYK2 signaling...
  5. Wang S, Chen Y, Kou R, Wang Y, Zeng T, Xie K, et al. Carbon disulfide activates p62-Nrf2-keap1 pathway in rat nerve tissues. Toxicology. 2016;368-369:19-27 pubmed publisher
    ..In addition, CS2 also lead to the activation of CAMKK2 and ULK1 kinase signaling in rat spinal cords and sciatic nerves...
  6. Cheng L, Wu Q, Kortenoeven M, Pisitkun T, Fenton R. A Systems Level Analysis of Vasopressin-mediated Signaling Networks in Kidney Distal Convoluted Tubule Cells. Sci Rep. 2015;5:12829 pubmed publisher
    ..Network analysis implicated phosphatidylinositol-4,5-bisphosphate 3-kinase or CAMKK dependent pathways in VP-mediated signaling; pharmacological inhibition of which significantly reduced dDAVP ..
  7. Yang W, Liao T, Bao Z, Zhou C, Luo H, Lu C, et al. Role of AMPK in the expression of tight junction proteins in heat-treated porcine Sertoli cells. Theriogenology. 2018;121:42-52 pubmed publisher
    ..AMPK phosphorylation, the cellular ATP level, and Ca2+/calmodulin-dependent protein kinase kinase B (CaMKKB) level, but not the liver kinase B1 (LKB1) level, were downregulated by heat treatment...
  8. Yuan L, Wang H, Liu Q, Wang Z, Zhang M, Zhao Y, et al. Etoposide-induced protein 2.4 functions as a regulator of the calcium ATPase and protects pancreatic β-cell survival. J Biol Chem. 2018;293:10128-10140 pubmed publisher
    ..ATP2a2, disrupted calcium homeostasis, and deactivated the calcium/calmodulin-dependent protein kinase kinase 2 (CAMKK2)-AMP-activated protein kinase (AMPK) pathway...
  9. Li S, Miller C, Giannopoulou E, Hu X, Ivashkiv L, Zhao B. RBP-J imposes a requirement for ITAM-mediated costimulation of osteoclastogenesis. J Clin Invest. 2014;124:5057-73 pubmed publisher
    ..and c-FOS by inhibiting ITAM-mediated expression and function of PLCγ2 and activation of downstream calcium-CaMKK/PYK2 signaling...
  10. Beck A, Isaac R, Lavelin I, Hart Y, Volberg T, Shatz Azoulay H, 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;54:2845-55 pubmed publisher
    ..with high confidence the involvement of several novel genes in cytokine-induced beta cell death, including Camkk2, Epn3, Foxp3 and Tm7sf3, which encodes an orphan seven transmembrane receptor...
  11. Duan J, Cui J, Yang Z, Guo C, Cao J, Xi M, et al. Neuroprotective effect of Apelin 13 on ischemic stroke by activating AMPK/GSK-3β/Nrf2 signaling. J Neuroinflammation. 2019;16:24 pubmed publisher
    ..Using selective inhibitors, we further identified the upstream of AMPK/GSK-3β/Nrf2 is AR/Gα/PLC/IP3/CaMKK. In conclusion, the previous results showed that Apelin 13 protected against I/R-induced ROS-mediated inflammation ..
  12. Li S, Yan Y, Jiao Y, Gao Z, Xia Y, Kong L, et al. Neuroprotective Effect of Osthole on Neuron Synapses in an Alzheimer's Disease Cell Model via Upregulation of MicroRNA-9. J Mol Neurosci. 2016;60:71-81 pubmed publisher
    ..cells, which was attributed to increases in microRNA-9 (miR-9) expression and subsequent decreases in CAMKK2 and p-AMPK? expressions...
  13. Kang S, Huang J, Lee B, Jung Y, Im E, Koh J, et al. Omega-3 polyunsaturated fatty acids protect human hepatoma cells from developing steatosis through FFA4 (GPR120). Biochim Biophys Acta Mol Cell Biol Lipids. 2018;1863:105-116 pubmed publisher
    ..In addition, DHA-induced activations of Gq/11 proteins, CaMKK, and AMPK were found to be signaling components of the steatosis protective pathway...
  14. Sundararaman A, Amirtham U, Rangarajan A. Calcium-Oxidant Signaling Network Regulates AMP-activated Protein Kinase (AMPK) Activation upon Matrix Deprivation. J Biol Chem. 2016;291:14410-29 pubmed publisher
    ..that the upstream AMPK kinases liver kinase B1 (LKB1) and Ca(2+)/calmodulin-dependent protein kinase kinase ? (CaMKK?) contribute to AMPK activation upon detachment...
  15. Ma Z, Wen D, Wang X, Yang L, Liu T, Liu J, et al. Growth inhibition of human gastric adenocarcinoma cells in vitro by STO-609 is independent of calcium/calmodulin-dependent protein kinase kinase-beta and adenosine monophosphate-activated protein kinase. Am J Transl Res. 2016;8:1164-71 pubmed
    ..Interestingly, we found such effects of STO-609 on gastric cancer cells were not affected after the knock-down of CaMKK-? and AMPK. In conclusion, STO-609 is an effective cytotoxic agent for gastric adenocarcinoma in vivo.
  16. Yung M, Ross F, Hardie D, Leung T, Zhan J, Ngan H, et al. Bitter Melon (Momordica charantia) Extract Inhibits Tumorigenicity and Overcomes Cisplatin-Resistance in Ovarian Cancer Cells Through Targeting AMPK Signaling Cascade. Integr Cancer Ther. 2016;15:376-89 pubmed publisher
    ..molecular mechanism demonstrated that BME activates AMP-activated protein kinase (AMPK) in an AMP-independent but CaMKK (Ca(2+)/calmodulin-dependent protein kinase)-dependent manner, exerting anticancer effects through activation of ..
  17. Balasubramanian R, Maruoka H, Jayasekara P, Gao Z, Jacobson K. AMP-activated protein kinase as regulator of P2Y(6) receptor-induced insulin secretion in mouse pancreatic β-cells. Biochem Pharmacol. 2013;85:991-8 pubmed publisher
    ..Calcium chelator BAPTA-AM, calmodulin-dependent protein kinase kinase (CaMKK) inhibitor STO-069 and IP3 receptor antagonist 2-APB attenuated P2Y6R-mediated AMPK phosphorylation revealing ..
  18. Yao C, Pang D, Lu C, Xu A, Huang P, Ouyang H, et al. Data Mining and Validation of AMPK Pathway as a Novel Candidate Role Affecting Intramuscular Fat Content in Pigs. Animals (Basel). 2019;9: pubmed publisher
    ..Western blot analysis further confirmed that LKB1/CaMKK2-AMPK-ACC1-CPT1A axis dominates the activity of AMPK signaling pathway...
  19. Huang Q, Cao H, Zhan L, Sun X, Wang G, Li J, et al. Mitochondrial fission forms a positive feedback loop with cytosolic calcium signaling pathway to promote autophagy in hepatocellular carcinoma cells. Cancer Lett. 2017;403:108-118 pubmed publisher
    ..Moreover, the positive feedback loop significantly promoted HCC cell global autophagy by Ca2+/CAMKK/AMPK pathway...
  20. Truvé K, Dickinson P, Xiong A, York D, Jayashankar K, Pielberg G, et al. Utilizing the Dog Genome in the Search for Novel Candidate Genes Involved in Glioma Development-Genome Wide Association Mapping followed by Targeted Massive Parallel Sequencing Identifies a Strongly Associated Locus. PLoS Genet. 2016;12:e1006000 pubmed publisher
    ..We identified three candidate genes that were highly associated with glioma susceptibility: CAMKK2, P2RX7 and DENR...
  21. Saunier E, Antonio S, Regazzetti A, Auzeil N, Laprevote O, Shay J, et al. Resveratrol reverses the Warburg effect by targeting the pyruvate dehydrogenase complex in colon cancer cells. Sci Rep. 2017;7:6945 pubmed publisher
    ..We further demonstrate that the inhibition of the CamKKB or the downstream AMPK pathway partly abolished the resveratrol-induced increase of glucose oxidation...
  22. Hamada T, Souda M, Yoshimura T, Sasaguri S, Hatanaka K, Tasaki T, et al. Anti-apoptotic effects of PCP4/PEP19 in human breast cancer cell lines: a novel oncotarget. Oncotarget. 2014;5:6076-86 pubmed
    ..b>CaMKK2 knockdown moderately decreased phospho-Akt(Thr308) and increased apoptosis in MCF-7 cells but not in SK-BR-3 cells...
  23. Andrews Z. Central mechanisms involved in the orexigenic actions of ghrelin. Peptides. 2011;32:2248-55 pubmed publisher
    ..The downstream signaling involves a novel CaMKK-AMPK-CPT1-UCP2 pathway that enhances mitochondrial efficiency and buffers reactive oxygen species in order to ..
  24. Bonàs Guarch S, Guindo Martinez M, Miguel Escalada I, Grarup N, Sebastian D, Rodríguez Fos E, et al. Re-analysis of public genetic data reveals a rare X-chromosomal variant associated with type 2 diabetes. Nat Commun. 2018;9:321 pubmed publisher
    ..for 70,127 subjects, we identify seven novel associated regions, five driven by common variants (LYPLAL1, NEUROG3, CAMKK2, ABO, and GIP genes), one by a low-frequency (EHMT2), and one driven by a rare variant in chromosome Xq23, ..
  25. Cohen S, Li B, Tsien R, Ma H. Evolutionary and functional perspectives on signaling from neuronal surface to nucleus. Biochem Biophys Res Commun. 2015;460:88-99 pubmed publisher
    ..dephosphorylates γCaMKII to dispatch it to the nucleus; and PP2A induces CaM release from γCaMKII so that CaMKK and CaMKIV can trigger CREB phosphorylation. Thus, while certain basic elements have been conserved from C...
  26. Santiago A, Couñago R, Ramos P, Godoi P, Massirer K, Gileadi O, et al. Structural Analysis of Inhibitor Binding to CAMKK1 Identifies Features Necessary for Design of Specific Inhibitors. Sci Rep. 2018;8:14800 pubmed publisher
    ..The structures reveal small but exploitable differences between CAMKK1 and CAMKK2, despite the high sequence identity, which could be used in the generation of specific inhibitors...
  27. Ma H, Groth R, Cohen S, Emery J, Li B, Hoedt E, et al. γCaMKII shuttles Ca²⁺/CaM to the nucleus to trigger CREB phosphorylation and gene expression. Cell. 2014;159:281-94 pubmed publisher
    ..Upon arrival within the nucleus, Ca(2+)/CaM activates CaMKK and its substrate CaMKIV, the CREB kinase...
  28. Dachtler J, Fox K. Do cortical plasticity mechanisms differ between males and females?. J Neurosci Res. 2017;95:518-526 pubmed publisher
    ..In particular, the CaMKK, NOS1 and estrogen receptor pathways show sexual dimorphisms with implications for plasticity in the hippocampus ..
  29. Xue W, Gu X, Wu Y, Li D, Xu Y, Wang H. Multiple regulatory aspects of histone methyltransferase EZH2 in Pb-induced neurotoxicity. Oncotarget. 2017;8:85169-85184 pubmed publisher
    ..respective response towards Pb treatment; EZH2 directly occupied the promoters of EGR2, NGFR and CaMKK2, genes responsible for various nerve functions and repair mechanisms, and essentially contributed to their ..
  30. Hall D, Cost N, Hegde S, Kellner E, Mikhaylova O, Stratton Y, et al. TRPM3 and miR-204 establish a regulatory circuit that controls oncogenic autophagy in clear cell renal cell carcinoma. Cancer Cell. 2014;26:738-53 pubmed publisher
    ..Increased expression of TRPM3 in RCC leads to Ca(2+) influx, activation of CAMKK2, AMPK, and ULK1, and phagophore formation...
  31. Penfold L, Woods A, Muckett P, Nikitin A, Kent T, Zhang S, et al. CAMKK2 Promotes Prostate Cancer Independently of AMPK via Increased Lipogenesis. Cancer Res. 2018;78:6747-6761 pubmed publisher
    ..Previous studies reported that calcium/calmodulin-dependent protein kinase kinase 2 (CAMKK2) expression is increased in human prostate cancer...
  32. da Silva Krause M, Bittencourt A, Homem de Bittencourt P, McClenaghan N, Flatt P, Murphy C, et al. Physiological concentrations of interleukin-6 directly promote insulin secretion, signal transduction, nitric oxide release, and redox status in a clonal pancreatic β-cell line and mouse islets. J Endocrinol. 2012;214:301-11 pubmed
    ..Calmodulin-dependent protein kinase kinase levels (CaMKK), an upstream kinase activator of AMPK, were also increased by 50% after IL6 exposure (in β-cells and islets)...
  33. Liu L, McCullough L, Li J. Genetic deletion of calcium/calmodulin-dependent protein kinase kinase β (CaMKK β) or CaMK IV exacerbates stroke outcomes in ovariectomized (OVXed) female mice. BMC Neurosci. 2014;15:118 pubmed publisher
    ..Calcium/calmodulin-dependent protein kinase kinase (CaMKK) is a major kinase that is activated by elevated intracellular calcium...
  34. Asquith C, Godoi P, Couñago R, Laitinen T, Scott J, Langendorf C, et al. 1,2,6-Thiadiazinones as Novel Narrow Spectrum Calcium/Calmodulin-Dependent Protein Kinase Kinase 2 (CaMKK2) Inhibitors. Molecules. 2018;23: pubmed publisher
    ..3,5-bis(arylamino)-4H-1,2,6-thiadiazin-4-one bound to calcium/calmodulin-dependent protein kinase kinase 2 (CaMKK2), several analogues were identified with micromolar activity through targeted displacement of bound water ..
  35. Jacquel A, Luciano F, Robert G, Auberger P. Implication and Regulation of AMPK during Physiological and Pathological Myeloid Differentiation. Int J Mol Sci. 2018;19: pubmed publisher
    ..kinases, the tumor suppressor liver kinase B1 (LKB1) and the calcium/calmodulin-dependent protein kinase kinase 2 (CAMKK2) through phosphorylation of the kinase on Thr172, leading to its activation...
  36. Yang S, Wang J. Estrogen Activates AMP-Activated Protein Kinase in Human Endothelial Cells via ERβ/Ca(2+)/Calmodulin-Dependent Protein Kinase Kinase β Pathway. Cell Biochem Biophys. 2015;72:701-7 pubmed publisher
    ..It is controlled by upstream kinases such as Ca(2+)/calmodulin-dependent protein kinase kinase β (CaMKKβ) or LKB1...
  37. Bowdridge E, Goravanahally M, Inskeep E, Flores J. Activation of Adenosine Monophosphate-Activated Protein Kinase Is an Additional Mechanism That Participates in Mediating Inhibitory Actions of Prostaglandin F2Alpha in Mature, but Not Developing, Bovine Corpora Lutea. Biol Reprod. 2015;93:7 pubmed publisher
    ..The objectives of this study were to determine 1) if calcium/calmodulin-dependent kinase kinase 2 (CAMKK2) participates in mediating PGF2alpha actions in developing (Day [d]-4) and mature (d-10) bovine corpus luteum (CL),..
  38. Kimura T, Tomura H, Sato K, Ito M, Matsuoka I, Im D, et al. Mechanism and role of high density lipoprotein-induced activation of AMP-activated protein kinase in endothelial cells. J Biol Chem. 2010;285:4387-97 pubmed publisher
    ..Several HDL-induced antiatherogenic actions are regulated by AMPK, but proliferation-related actions are regulated by Ras rather than AMPK. ..
  39. Davie E, Forte G, Petersen J. Nitrogen regulates AMPK to control TORC1 signaling. Curr Biol. 2015;25:445-54 pubmed publisher
    ..The CaMKK homolog Ssp1 is constitutively required for phosphorylation of the AMPKα(Ssp2) T loop...
  40. Price D, Drewry D, Schaller L, Thompson B, Reid P, Maloney P, et al. An orally available, brain-penetrant CAMKK2 inhibitor reduces food intake in rodent model. Bioorg Med Chem Lett. 2018;28:1958-1963 pubmed publisher
    Hypothalamic CAMKK2 represents a potential mechanism for chemically affecting satiety and promoting weight loss in clinically obese patients...
  41. Antonia R, Baldwin A. IKK promotes cytokine-induced and cancer-associated AMPK activity and attenuates phenformin-induced cell death in LKB1-deficient cells. Sci Signal. 2018;11: pubmed publisher
    ..sensor that is activated upon phosphorylation of Thr172 in its activation loop by the kinase LKB1, CAMKK2, or TAK1...
  42. Kawashima J, Alquier T, Tsuji Y, Peroni O, Kahn B. Ca2+/calmodulin-dependent protein kinase kinase is not involved in hypothalamic AMP-activated protein kinase activation by neuroglucopenia. PLoS ONE. 2012;7:e36335 pubmed publisher
    ..kinases that activate AMPK have been identified including Ca(2+)/Calmodulin-dependent protein kinase kinase (CaMKK), which is highly expressed in neurons...
  43. Guimond D, Diabira D, Porcher C, Bader F, Ferrand N, Zhu M, et al. Leptin potentiates GABAergic synaptic transmission in the developing rodent hippocampus. Front Cell Neurosci. 2014;8:235 pubmed publisher
    ..MAPK/ERK kinases 1 and/or 2 (MEK1/2), phosphoinositide 3 kinase (PI3K) and calcium-calmodulin kinase kinase (CaMKK)...
  44. Ramos Lopez O, Samblas M, Milagro F, Zulet M, Mansego M, Riezu Boj J, et al. Association of low dietary folate intake with lower CAMKK2 gene methylation, adiposity, and insulin resistance in obese subjects. Nutr Res. 2018;50:53-62 pubmed publisher
    ..The calcium/calmodulin-dependent protein kinase kinase 2 (CAMKK2) is involved in the regulation of critical metabolic processes such as adiposity and glucose homeostasis...
  45. Tojkander S, Ciuba K, Lappalainen P. CaMKK2 Regulates Mechanosensitive Assembly of Contractile Actin Stress Fibers. Cell Rep. 2018;24:11-19 pubmed publisher
    ..Here, we identify Ca2+-calmodulin-dependent kinase kinase 2 (CaMKK2) as a critical upstream factor controlling mechanosensitive AMPK activation...
  46. Sayad A, Ranjbaran F, Ghafouri Fard S, Arsang Jang S, Taheri M. Expression Analysis of CYFIP1 and CAMKK2 Genes in the Blood of Epileptic and Schizophrenic Patients. J Mol Neurosci. 2018;65:336-342 pubmed publisher
    ..In the present case-control study, we have assessed expression of CYFIP1 and CAMKK2 genes in the blood samples of epileptic and schizophrenic patients compared with healthy subjects...
  47. Hutchins B, Wray S. Capture of microtubule plus-ends at the actin cortex promotes axophilic neuronal migration by enhancing microtubule tension in the leading process. Front Cell Neurosci. 2014;8:400 pubmed publisher
    ..leading process actin flow in migrating GnRH neurons is controlled by a signaling cascade involving IP3 receptors, CaMKK, AMPK, and RhoA. In the present study, microtubule dynamics were examined in GnRH neurons...
  48. Zhang Y, Xu N, Ding Y, Zhang Y, Li Q, Flores J, et al. Chemerin suppresses neuroinflammation and improves neurological recovery via CaMKK2/AMPK/Nrf2 pathway after germinal matrix hemorrhage in neonatal rats. Brain Behav Immun. 2018;70:179-193 pubmed publisher
    ..its natural receptor, ChemR23, as well as its downstream mediator calmodulin-dependent protein kinase kinase 2 (CAMKK2)/adenosine monophosphate-activated protein kinase (AMPK) /Nuclear factor erythroid 2-related factor 2 (Nrf2) ..
  49. Saito A, Miyajima K, Akatsuka J, Kondo H, Mashiko T, Kiuchi T, et al. CaMKII?-mediated LIM-kinase activation plays a crucial role in BDNF-induced neuritogenesis. Genes Cells. 2013;18:533-43 pubmed publisher
    ..of Ca(2+) /calmodulin-dependent protein kinases (CaMKs), but not by STO-609, an inhibitor of CaMK-kinase (CaMKK)...
  50. Horigane S, Ageta Ishihara N, Kamijo S, Fujii H, Okamura M, Kinoshita M, et al. Facilitation of axon outgrowth via a Wnt5a-CaMKK-CaMKIα pathway during neuronal polarization. Mol Brain. 2016;9:8 pubmed publisher
    ..Pharmacological and genetic inhibition of the CaMKK-CaMKIα pathway abolished Wnt5a-induced axonal elongation, and rescue of CaMKIα in CaMKIα-knockdown ..
  51. Leem J, Shim H, Cho H, Park J. Octanoic acid potentiates glucose-stimulated insulin secretion and expression of glucokinase through the olfactory receptor in pancreatic β-cells. Biochem Biophys Res Commun. 2018;503:278-284 pubmed publisher
    ..was blocked by an IP3R antagonist and a Ca2+/calmodulin-dependent protein kinase kinase (CaMKK) inhibitor...
  52. Neumann D. Is TAK1 a Direct Upstream Kinase of AMPK?. Int J Mol Sci. 2018;19: pubmed publisher
    Alongside Liver kinase B1 (LKB1) and Ca2+/Calmodulin-dependent protein kinase kinase 2 (CaMKK2), Transforming growth factor-β (TGF-β)-activated kinase 1 (TAK1) has been suggested as a direct upstream kinase of AMP-activated ..
  53. Fujiwara Y, Hiraoka Y, Fujimoto T, Kanayama N, Magari M, Tokumitsu H. Analysis of Distinct Roles of CaMKK Isoforms Using STO-609-Resistant Mutants in Living Cells. Biochemistry. 2015;54:3969-77 pubmed publisher
    To assess the isoform specificity of the Ca(2+)/calmodulin-dependent protein kinase kinase (CaMKK)-mediated signaling pathway using a CaMKK inhibitor (STO-609) in living cells, we have established A549 cell lines expressing STO-609-..
  54. Cheng S, So W, Zhang D, Cheng Q, Boucher B, Leung P. Calcitriol Reduces Hepatic Triglyceride Accumulation and Glucose Output Through Ca2+/CaMKKβ/AMPK Activation Under Insulin-Resistant Conditions in Type 2 Diabetes Mellitus. Curr Mol Med. 2016;16:747-758 pubmed
    ..AMPK/ACC) phosphorylation via the Ca2+/calmodulin-dependent protein kinase kinase β (CaMKKβ) pathway, contributing to the reductions in hepatic triglyceride accumulation and glucose output...
  55. Martinelli R, Gegg M, Longbottom R, Adamson P, Turowski P, Greenwood J. ICAM-1-mediated endothelial nitric oxide synthase activation via calcium and AMP-activated protein kinase is required for transendothelial lymphocyte migration. Mol Biol Cell. 2009;20:995-1005 pubmed publisher
    ..of eNOS on S1177 in response to ICAM-1 activation was regulated by src family protein kinase, rho GTPase, Ca(2+), CaMKK, and AMPK, but not Akt/PI3K...
  56. Pritchard Z, Cary R, Yang C, Novack D, Voor M, Sankar U. Inhibition of CaMKK2 reverses age-associated decline in bone mass. Bone. 2015;75:120-7 pubmed publisher
    ..ablation of the tissue-restricted and multifunctional Ca(2+)/calmodulin (CaM)-dependent protein kinase kinase 2 (CaMKK2) stimulates trabecular bone mass accrual, mainly by promoting anabolic pathways and inhibiting catabolic pathways ..
  57. Chen S, Dong Z, Yang P, Wang X, Jin G, Yu H, et al. Hepatitis B virus X protein stimulates high mobility group box 1 secretion and enhances hepatocellular carcinoma metastasis. Cancer Lett. 2017;394:22-32 pubmed publisher
    ..HBx triggered an increase of cytoplasmic calcium and activated CAMKK/CAMKIV pathway, leading to subsequent translocation and release of HMGB1...
  58. Popovics P, Frigo D, Schally A, Rick F. Targeting the 5'-AMP-activated protein kinase and related metabolic pathways for the treatment of prostate cancer. Expert Opin Ther Targets. 2015;19:617-32 pubmed publisher
    ..of AMPK by androgens and upstream kinases including the calcium/calmodulin-dependent protein kinase kinase 2 (CaMKK2) in prostate cancer. Oncogenic, AMPK-regulated pathways that direct various metabolic processes are also addressed...
  59. MacDonald A, Bettaieb A, Donohoe D, Alani D, Han A, Zhao Y, et al. Concurrent regulation of LKB1 and CaMKK2 in the activation of AMPK in castrate-resistant prostate cancer by a well-defined polyherbal mixture with anticancer properties. BMC Complement Altern Med. 2018;18:188 pubmed publisher
    ..are known to activate AMPK: liver kinase B1 (LKB1), a tumor suppressor, and calcium-calmodulin kinase kinase-2 (CaMKK2), a tumor promotor over-expressed in many cancers...
  60. Wang M, Wu H, Huang S, Zhang H, Qin C, Zhao L, et al. HBx regulates fatty acid oxidation to promote hepatocellular carcinoma survival during metabolic stress. Oncotarget. 2016;7:6711-26 pubmed publisher
    ..stimulated phosphorylation of AMP-activated protein kinase (AMPK) and acetyl-CoA carboxylase (ACC) via a calcium/CaMKK-dependent pathway, which was required for the activation of FAO...
  61. Banerjee S, Ghoshal S, Porter T. Activation of AMP-kinase by policosanol requires peroxisomal metabolism. Lipids. 2011;46:311-21 pubmed publisher
    ..AMP-kinase and HMG-CoA reductase, and increased the phosphorylation of Ca(++)/calmodulin-dependent kinase kinase (CaMKK), an upstream AMP-kinase kinase...
  62. Anderson C, Kendig D, Al Qudah M, Mahavadi S, Murthy K, Grider J. Role of various kinases in muscarinic M3 receptor-mediated contraction of longitudinal muscle of rat colon. J Smooth Muscle Res. 2014;50:103-19 pubmed publisher
    ..Basal tension was differentially regulated by Rho kinase, ERK1/2, CaMKII and CaMKK. Selective inhibitors of Rho kinase, ERK1/2, CaMKK/AMPK, and CaMKII each reduced carbachol-induced contraction in ..
  63. Senga Y, Ishida A, Shigeri Y, Kameshita I, Sueyoshi N. The Phosphatase-Resistant Isoform of CaMKI, Ca²⁺/Calmodulin-Dependent Protein Kinase Iδ (CaMKIδ), Remains in Its "Primed" Form without Ca²⁺ Stimulation. Biochemistry. 2015;54:3617-30 pubmed publisher
    ..CaMKI is activated through phosphorylation by the upstream kinase, CaMK kinase (CaMKK), and phosphorylates downstream targets...
  64. Liu L, Yuan H, Denton K, Li X, McCullough L, Li J. Calcium/calmodulin-dependent protein kinase kinase β is neuroprotective in stroke in aged mice. Eur J Neurosci. 2016;44:2139-46 pubmed publisher
    ..Calcium/calmodulin-dependent protein kinase kinase β (CaMKK β) is a major kinase activated by elevated levels of intracellular calcium...
  65. Ha T, Burwell S, Goodwin M, Noeker J, Heggland S. Pleiotropic roles of Ca+2/calmodulin-dependent pathways in regulating cadmium-induced toxicity in human osteoblast-like cell lines. Toxicol Lett. 2016;260:18-27 pubmed publisher
    ..with calmodulin-dependent phosphodiesterase (PDE) inhibitor CGS-9343?; calmodulin-dependent kinase kinase (CAMKK) inhibitor STO-609; or calmodulin-dependent kinase II (CAMKII) inhibitor KN-93...
  66. Goullee H, Wadley A, Cherry C, Allcock R, Black M, Kamerman P, et al. Polymorphisms in CAMKK2 may predict sensory neuropathy in African HIV patients. J Neurovirol. 2016;22:508-17 pubmed publisher
    ..polymorphisms (SNPs) in a cluster of three genes that affect inflammation and neuronal repair: P2X7R, P2X4R and CAMKK2. HIV-SN status was assessed using the Brief Peripheral Neuropathy Screening tool, with SN defined by bilateral ..
  67. Wang B, Wu Z, Ji Y, Sun K, Dai Z, Wu G. L-Glutamine Enhances Tight Junction Integrity by Activating CaMK Kinase 2-AMP-Activated Protein Kinase Signaling in Intestinal Porcine Epithelial Cells. J Nutr. 2016;146:501-8 pubmed publisher
    ..conducted to test the hypothesis that Gln regulates TJ integrity through calcium/calmodulin-dependent kinase 2 (CaMKK2)-AMP-activated protein kinase (AMPK) signaling which, in turn, contributes to improved intestinal mucosal barrier ..
  68. Kanno Y, Ishisaki A, Kawashita E, Kuretake H, Ikeda K, Matsuo O. uPA Attenuated LPS-induced Inflammatory Osteoclastogenesis through the Plasmin/PAR-1/Ca(2+)/CaMKK/AMPK Axis. Int J Biol Sci. 2016;12:63-71 pubmed publisher
    ..monophosphate-activated protein kinase (AMPK) pathway through Ca2+/calmodulin dependent protein kinase kinase (CaMKK) activation, and attenuated inflammatory osteoclastogenesis by inactivation of NF-κB in RAW264.7 cells...
  69. Gocher A, Azabdaftari G, Euscher L, Dai S, Karacosta L, Franke T, et al. Akt activation by Ca2+/calmodulin-dependent protein kinase kinase 2 (CaMKK2) in ovarian cancer cells. J Biol Chem. 2017;292:14188-14204 pubmed publisher
    ..We observed that Ca2+/calmodulin (CaM)-dependent protein kinase kinase 2 (?) (CaMKK2) is highly expressed in high-grade serous ovarian cancer, and we investigated its role in Akt activation in ..
  70. Wang N, Yao M, Xu J, Quan Y, Zhang K, Yang R, et al. Autocrine Activation of CHRM3 Promotes Prostate Cancer Growth and Castration Resistance via CaM/CaMKK-Mediated Phosphorylation of Akt. Clin Cancer Res. 2015;21:4676-85 pubmed publisher
    ..we found that autocrine cholinergic signaling caused calmodulin/calmodulin-dependent protein kinase kinase (CaM/CaMKK)-mediated phosphorylation of Akt...
  71. Gaff J, Halstrom S, Temple S, Baltic S, Kamerman P, Price P. Polymorphisms in P2X4R and CAMKK2 may affect TNFα production: Implications for a role in HIV-associated sensory neuropathy. Hum Immunol. 2018;79:224-227 pubmed publisher
    Polymorphisms in P2X4R and CAMKK2 associate with susceptibility to HIV-associated sensory neuropathy (HIV-SN) - a condition likely mediated by TNFα...
  72. Obba S, Hizir Z, Boyer L, Selimoglu Buet D, Pfeifer A, Michel G, et al. The PRKAA1/AMPKα1 pathway triggers autophagy during CSF1-induced human monocyte differentiation and is a potential target in CMML. Autophagy. 2015;11:1114-29 pubmed publisher
    ..Here we show that the CAMKK2-PRKAA1-ULK1 pathway is required for CSF1-induced autophagy and human monocyte differentiation...
  73. Shaw G, Whitaker H, Corcoran M, Dunning M, Luxton H, Kay J, et al. The Early Effects of Rapid Androgen Deprivation on Human Prostate Cancer. Eur Urol. 2016;70:214-8 pubmed publisher
    ..We observed differential expression of known androgen-regulated genes (TMPRSS2, KLK3, CAMKK2, FKBP5). We identified 749 genes downregulated and 908 genes upregulated following castration...
  74. Yu H, Zhang H, Dong M, Wu Z, Shen Z, Xie Y, et al. Metabolic reprogramming and AMPK?1 pathway activation by caulerpin in colorectal cancer cells. Int J Oncol. 2017;50:161-172 pubmed publisher
    ..protein kinase (AMPK) was activated by caulerpin treatment in a calcium/calmodulin-dependent protein kinase 2 (CaMKK2)?dependent manner...
  75. Sinha R, Singh B, Zhou J, Wu Y, Farah B, Ohba K, et al. Thyroid hormone induction of mitochondrial activity is coupled to mitophagy via ROS-AMPK-ULK1 signaling. Autophagy. 2015;11:1341-57 pubmed publisher
    ..We show that T3 induction of ROS activates CAMKK2 (calcium/calmodulin-dependent protein kinase kinase 2, β) mediated phosphorylation of PRKAA1/AMPK (5' AMP-..
  76. O Brien M, Oakhill J, Ling N, Langendorf C, Hoque A, Dite T, et al. Impact of Genetic Variation on Human CaMKK2 Regulation by Ca2+-Calmodulin and Multisite Phosphorylation. Sci Rep. 2017;7:43264 pubmed publisher
    The Ca2+-calmodulin dependent protein kinase kinase-2 (CaMKK2) is a key regulator of neuronal function and whole-body energy metabolism...
  77. Sankar U, Pritchard Z, Voor M. Micro-computed tomography assisted distal femur metaphyseal blunt punch compression for determining trabecular bone strength in mice. J Biomech. 2016;49:1233-1237 pubmed publisher
    ..system consisting of five month old male wild-type (WT) and Ca(2+)/calmodulin dependent protein kinase kinase 2 (CaMKK2) knockout (KO) Camkk2(-/-) mice that possess recorded differences in trabecular bone volume, data collected using ..
  78. Psenakova K, Petrvalska O, Kylarova S, Lentini Santo D, Kalabova D, Herman P, et al. 14-3-3 protein directly interacts with the kinase domain of calcium/calmodulin-dependent protein kinase kinase (CaMKK2). Biochim Biophys Acta Gen Subj. 2018;1862:1612-1625 pubmed publisher
    Calcium/calmodulin-dependent protein kinase kinase 2 (CaMKK2) is a member of the Ca2+/calmodulin-dependent kinase (CaMK) family involved in adiposity regulation, glucose homeostasis and cancer...
  79. Fogarty S, Ross F, Vara Ciruelos D, Gray A, Gowans G, Hardie D. AMPK Causes Cell Cycle Arrest in LKB1-Deficient Cells via Activation of CAMKK2. Mol Cancer Res. 2016;14:683-95 pubmed publisher
    ..by the tumor suppressor kinase LKB1 or by an alternate pathway involving the Ca(2+)/calmodulin-dependent kinase, CAMKK2. Increases in AMP:ATP and ADP:ATP ratios, signifying energy deficit, promote allosteric activation and net Thr172 ..
  80. Moss B, Park L, Dahlberg C, Juo P. The CaM Kinase CMK-1 Mediates a Negative Feedback Mechanism Coupling the C. elegans Glutamate Receptor GLR-1 with Its Own Transcription. PLoS Genet. 2016;12:e1006180 pubmed publisher
    ..Loss-of-function mutations in the upstream kinase ckk-1/CaMKK, the CaM kinase cmk-1/CaMK, or a downstream transcription factor crh-1/CREB, result in increased glr-1 ..
  81. Ye C, Zhang D, Zhao L, Li Y, Yao X, Zhang S, et al. CaMKK2 Suppresses Muscle Regeneration through the Inhibition of Myoblast Proliferation and Differentiation. Int J Mol Sci. 2016;17: pubmed
    ..Therefore, a deeper understanding of muscle regeneration is needed to provide a new insight for new therapies. CaMKK2 plays a role in the calcium/calmodulin-dependent kinase cascade; however, its role in skeletal muscle remains ..
  82. Takata T, Ihara H, Hatano N, Tsuchiya Y, Akaike T, Watanabe Y. Reactive sulfur species inactivate Ca2+/calmodulin-dependent protein kinase IV via S-polysulfidation of its active-site cysteine residue. Biochem J. 2017;474:2547-2562 pubmed publisher
    ..CaMKIV is phosphorylated at Thr196 by its upstream CaMK kinase (CaMKK), resulting in the induction of its full activity...
  83. Atakhorrami M, Rahimi Aliabadi S, Jamshidi J, Moslemi E, Movafagh A, Ohadi M, et al. A genetic variant in CAMKK2 gene is possibly associated with increased risk of bipolar disorder. J Neural Transm (Vienna). 2016;123:323-8 pubmed publisher
    A recent large-scale study have reported that rs1063843, a single nucleotide polymorphism located in the CAMKK2 gene is highly associated with schizophrenia in European and Han Chinese populations...
  84. Kim Y, Lim J, Kim M, Kim E, Yoon H, Shin S, et al. The Adiponectin Receptor Agonist AdipoRon Ameliorates Diabetic Nephropathy in a Model of Type 2 Diabetes. J Am Soc Nephrol. 2018;29:1108-1127 pubmed publisher
    ..Expression of AdipoR1, AdipoR2, and Ca2+/calmodulin-dependent protein kinase kinase-β (CaMKKβ) and numbers of phosphorylated liver kinase B1 (LKB1)- and AMPK-positive cells significantly decreased in ..
  85. Kim N, Lee J, Lee H, Lee Y, Kim H, Kim S, et al. AMPK, a metabolic sensor, is involved in isoeugenol-induced glucose uptake in muscle cells. J Endocrinol. 2016;228:105-14 pubmed publisher
    ..and glucose uptake was inhibited by STO-609, an inhibitor of calcium/calmodulin-dependent protein kinase kinase (CaMKK). Isoeugenol also increased the phosphorylation of protein kinase C-α (PKCα)...
  86. Deng L, Lee M, Schutt K, Moseley J. Phosphatases Generate Signal Specificity Downstream of Ssp1 Kinase in Fission Yeast. Mol Cell Biol. 2017;37: pubmed publisher
    ..In the fission yeast Schizosaccharomyces pombe, the CaMKK-like protein kinase Ssp1 promotes cell cycle progression by activating the ARK Cdr2 according to cell growth ..
  87. Lin F, Marcelo K, Rajapakshe K, Coarfa C, Dean A, Wilganowski N, et al. The camKK2/camKIV relay is an essential regulator of hepatic cancer. Hepatology. 2015;62:505-20 pubmed publisher
    ..Here, we report that the expression of Ca(2+) /calmodulin-dependent protein kinase kinase 2 (CaMKK2) is significantly up-regulated in hepatocellular carcinoma (HCC) and negatively correlated with HCC patient ..
  88. Jin L, Chun J, Pan C, Kumar A, Zhang G, Ha Y, et al. The PLAG1-GDH1 Axis Promotes Anoikis Resistance and Tumor Metastasis through CamKK2-AMPK Signaling in LKB1-Deficient Lung Cancer. Mol Cell. 2018;69:87-99.e7 pubmed publisher
    ..Mechanistically, the GDH1 product α-KG activates CamKK2 by enhancing its substrate AMPK binding, which contributes to energy production that confers anoikis resistance...
  89. Marcelo K, Means A, York B. The Ca(2+)/Calmodulin/CaMKK2 Axis: Nature's Metabolic CaMshaft. Trends Endocrinol Metab. 2016;27:706-718 pubmed publisher
    ..An appreciation of this information is critical to understanding the mechanisms by which Ca(2+)/CaM-dependent signaling contributes to metabolic homeostasis and disease. ..
  90. Junker J, Rief M. Single-molecule force spectroscopy distinguishes target binding modes of calmodulin. Proc Natl Acad Sci U S A. 2009;106:14361-6 pubmed publisher
    ..to CaM in a highly cooperative way, while only a lower degree of interdomain binding cooperativity emerges for CaMKK, a target peptide from CaM-dependent kinase kinase...
  91. Karacosta L, Foster B, Azabdaftari G, Feliciano D, Edelman A. A regulatory feedback loop between Ca2+/calmodulin-dependent protein kinase kinase 2 (CaMKK2) and the androgen receptor in prostate cancer progression. J Biol Chem. 2012;287:24832-43 pubmed publisher
    ..We report that Ca(2+)/calmodulin-dependent kinase kinase 2 (CaMKK2) expression increases and becomes nuclear or perinuclear in advanced PCa...
  92. Marcelo K, Ribar T, Means C, Tsimelzon A, Stevens R, Ilkayeva O, et al. Research Resource: Roles for Calcium/Calmodulin-Dependent Protein Kinase Kinase 2 (CaMKK2) in Systems Metabolism. Mol Endocrinol. 2016;30:557-72 pubmed publisher
    ..resource, we explore the metabolic functions and implications of Ca(2+)/CaM-dependent protein kinase kinase 2 (CaMKK2) as a metabolic effector of Ca(2+)/CaM action...