Calcium/calmodulin-dependent protein kinase kinase 2: Roles in signaling and pathophysiology

Journal of Biological Chemistry

Volumn 287, Issue 38, 2012, Pages 31658-31665

  Racioppi, Luigi ^a,b,c   Means, Anthony R ^a,b  

^a DUKE UNIVERSITY SCHOOL OF MEDICINE   (United States)

^b DUKE UNIVERSITY MEDICAL CENTER   (United States)

^c UNIVERSITY OF NAPLES FEDERICO II   (Italy)

Author keywords

[No Author keywords available]

Indexed keywords

AMP-ACTIVATED PROTEIN KINASE; CALCIUM/CALMODULIN-DEPENDENT PROTEIN KINASE; CELL EXPRESSION; GLUCOSE HOMEOSTASIS; INTRACELLULAR CA; PATHOPHYSIOLOGICAL; PATHOPHYSIOLOGY; SIGNALING CASCADES; THERAPEUTIC INTERVENTION;

CALCIUM; CAMS; ENZYME ACTIVITY; GLUCOSE; PHYSIOLOGY;

CALMODULIN;

CALCIUM CALMODULIN DEPENDENT PROTEIN KINASE KINASE; PROTEIN CAMKK2; UNCLASSIFIED DRUG;

ADIPOSE TISSUE; BONE MARROW CELL; BRAIN FUNCTION; ENZYME PHOSPHORYLATION; ENZYME STRUCTURE; GLUCOSE INTOLERANCE; HUMAN; LIVER PARENCHYMA; NONHUMAN; OBESITY; PATHOPHYSIOLOGY; PRIORITY JOURNAL; PROSTATE CANCER; PROTEIN EXPRESSION; PROTEIN FUNCTION; PROTEIN TARGETING; SHORT SURVEY; SIGNAL TRANSDUCTION;

ADIPOSE TISSUE; ADIPOSITY; AMP-ACTIVATED PROTEIN KINASES; ANIMALS; CALCIUM-CALMODULIN-DEPENDENT PROTEIN KINASE KINASE; FEMALE; GENE EXPRESSION REGULATION; GLUCOSE; HOMEOSTASIS; HUMANS; INFLAMMATION; LIVER; MACROPHAGES; MALE; MICE; NEURONS; PHOSPHORYLATION; PROSTATIC NEOPLASMS; RATS; SIGNAL TRANSDUCTION; TISSUE DISTRIBUTION;

EID: 84866404225     PISSN: 00219258     EISSN: 1083351X     Source Type: Journal    
DOI: 10.1074/jbc.R112.356485     Document Type: Short Survey

References (83)

1. Berridge, M. J. (2001) The versatility and complexity of calcium signaling. Novartis Found. Symp. 239, 52-64; discussion 64-57, 150-159
2. Chin, D., and Means, A. R. (2000) Calmodulin: a prototypical calcium sensor. Trends Cell Biol. 10, 322-328 (Pubitemid 30445239)
3. 2+/CaM-dependent kinases: from activation to function. Annu. Rev. Pharmacol. Toxicol. 41, 471-505
4. Soderling, T. R. (1999) The calcium/calmodulin-dependent protein kinase cascade. Trends Biochem. Sci. 24, 232-236
5. Hawley, S. A., Pan, D. A., Mustard, K. J., Ross, L., Bain, J., Edelman, A. M., Frenguelli, B. G., and Hardie, D. G. (2005) Calmodulin-dependent protein kinase kinase β is an alternative upstream kinase for AMP-activated protein kinase. Cell Metab. 2, 9-19 (Pubitemid 43239821)
6. 2+/ calmodulin-dependent protein kinase kinase β acts upstream of AMP-activated protein kinase in mammalian cells. Cell Metab. 2, 21-33
7. 2+/calmodulin-dependent protein kinase kinases are AMP-activated protein kinase kinases. J. Biol. Chem. 280, 29060-29066
8. Anderson, K. A., Ribar, T. J., Lin, F., Noeldner, P. K., Green, M. F., Muehlbauer, M. J., Witters, L. A., Kemp, B. E., and Means, A. R. (2008) Hypothalamic CaMKK2 contributes to the regulation of energy balance. Cell Metab. 7, 377-388 (Pubitemid 351598022)
9. 2+/calmodulin- dependent protein kinase IV. Identification of a brain CaM kinase IV kinase. J. Biol. Chem. 269, 28640-28647
10. 2+/calmodulin-dependent protein kinase kinase β. J. Biochem. 122, 243-250
11. 2+/calmodulin-dependent protein kinase cascade. Molecular cloning and expression of calcium/calmodulin-dependent protein kinase kinase. J. Biol. Chem. 270, 19320-19324
12. Anderson, K. A., Means, R. L., Huang, Q. H., Kemp, B. E., Goldstein, E. G., Selbert, M. A., Edelman, A. M., Fremeau, R. T., and Means, A. R. (1998) Components of a calmodulin-dependent protein kinase cascade. Molecular cloning, functional characterization, and cellular localization of Ca2+/calmodulin- dependent protein kinase kinase β. J. Biol. Chem. 273, 31880-31889 (Pubitemid 29177125)
13. 2+/calmodulin-dependent protein kinase kinase. J. Biomed. Sci. 5, 141-149
14. 2+/calmodulin-dependent protein kinase kinase β (CaMKKβ) and characterization of CaMKKβ and CaMKKα distribution in the adult mouse brain. Brain Res. Mol. Brain Res. 111, 216-221
15. Tokumitsu, H., Wayman, G. A., Muramatsu, M., and Soderling, T. R. (1997) Calcium/calmodulin-dependent protein kinase kinase: identification of regulatory domains. Biochemistry 36, 12823-12827 (Pubitemid 27465392)
16. 2+/calmodulin-dependent protein kinase kinase β gene encodes multiple isoforms that display distinct kinase activity. J. Biol. Chem. 276, 31113-31123
17. Cao, W., Sohail, M., Liu, G., Koumbadinga, G. A., Lobo, V. G., and Xie, J. (2011) Differential effects of PKA-controlled CaMKK2 variants on neuronal differentiation. RNA Biol. 8, 1061-1072
18. Deleted in proof
19. Tijssen, M. R., Cvejic, A., Joshi, A., Hannah, R. L., Ferreira, R., Forrai, A., Bellissimo, D. C., Oram, S. H., Smethurst, P. A., Wilson, N. K., Wang, X., Ottersbach, K., Stemple, D. L., Green, A. R., Ouwehand, W. H., and Göttgens, B. (2011) Genome-wide analysis of simultaneous GATA1/2, RUNX1, FLI1, and SCL binding in megakaryocytes identifies hematopoietic regulators. Dev. Cell 20, 597-609
20. Zagami, C. J., Zusso, M., and Stifani, S. (2009) Runx transcription factors: lineage-specific regulators of neuronal precursor cell proliferation and post-mitotic neuron subtype development. J. Cell Biochem. 107, 1063-1072
21. Inoue, K., Shiga, T., and Ito, Y. (2008) Runx transcription factors in neuronal development. Neural Dev. 3, 20
22. Teng, E. C., Racioppi, L., and Means, A. R. (2011) A cell-intrinsic role for CaMKK2 in granulocyte lineage commitment and differentiation. J. Leukocyte Biol. 90, 897-909
23. Kokubo, M., Nishio, M., Ribar, T. J., Anderson, K. A., West, A. E., and Means, A. R. (2009) BDNF-mediated cerebellar granule cell development is impaired in mice null for CaMKK2 or CaMKIV. J. Neurosci. 29, 8901-8913
24. Green, M. F., Anderson, K. A., and Means, A. R. (2011) Characterization of the CaMKKβ-AMPK signaling complex. Cell. Signal. 23, 2005-2012
25. 2+/calmodulin-dependent protein kinase kinase in complex with the inhibitor STO-609. J. Biol. Chem. 286, 22570-22579
26. 2+/calmodulin-dependent protein kinase kinase isoforms. Biochemistry 40, 13925-13932
27. 2+/calmodulin-dependent protein kinase kinase β is regulated by multisite phosphorylation. J. Biol. Chem. 286, 28066-28079
28. 2+/calmodulin-dependent protein kinase kinase β by autophosphorylation. Biochemistry 50, 8193-8201
29. Racioppi, L., and Means, A. R. (2008) Calcium/calmodulin-dependent kinase IV in immune and inflammatory responses: novel routes for an ancient traveler. Trends Immunol. 29, 600-607
30. Gong, S., Zheng, C., Doughty, M. L., Losos, K., Didkovsky, N., Schambra, U. B., Nowak, N. J., Joyner, A., Leblanc, G., Hatten, M. E., and Heintz, N. (2003) A gene expression atlas of the central nervous system based on bacterial artificial chromosomes. Nature 425, 917-925 (Pubitemid 37376918)
31. 2+/calmodulin-dependent protein kinase enriched in cerebellar granule cells. Identification of a novel neuronal calmodulin-dependent protein kinase. J. Biol. Chem. 264, 5866-5875
32. Anderson, K. A., Lin, F., Ribar, T. J., Stevens, R. D., Muehlbauer, M. J., Newgard, C. B., and Means, A. R. (2012) Deletion of CaMKK2 from the liver lowers blood glucose and improves whole body glucose tolerance in the mouse. Mol. Endocrinol. 26, 281-291
33. 2+/ calmodulin-dependent protein kinase kinase CaMKK2 inhibits preadipocyte differentiation. Endocrinology 152, 3668-3679
34. 2+/calmodulin-dependent protein kinase kinase β. Mol. Cell. Biol. 26, 5933-5945
35. Racioppi, L., Noeldner, P. K., Lin, F., Arvai, S., and Means, A. R. (2012) Calcium/calmodulin-dependent protein kinase kinase 2 regulates macrophagemediated inflammatory responses. J. Biol. Chem. 287, 11579-11591
36. Michaelsen, K., and Lohmann, C. (2010) Calcium dynamics at developing synapses: mechanisms and functions. Eur. J. Neurosci. 32, 218-223
37. Wayman, G. A., Lee, Y. S., Tokumitsu, H., Silva, A., and Soderling, T. R. (2008) Calmodulin kinases: modulators of neuronal development and plasticity. Neuron 59, 914-931
38. Takemoto-Kimura, S., Suzuki, K., Kamijo, S., Ageta-Ishihara, N., Fujii, H., Okuno, H., and Bito, H. (2010) Differential roles for CaM kinases in mediating excitation-morphogenesis coupling during formation and maturation of neuronal circuits. Eur. J. Neurosci. 32, 224-230
39. 2+/calmodulin kinase kinase β affects the formation of some, but not all, types of hippocampus-dependent long-term memory. J. Neurosci. 23, 9752-9760
40. Mizuno, K., Antunes-Martins, A., Ris, L., Peters, M., Godaux, E., and Giese, K. P. (2007) Calcium/calmodulin kinase kinase β has a male-specific role in memory formation. Neuroscience 145, 393-402 (Pubitemid 46341643)
41. 2+/calmodulin kinase kinase α is dispensable for brain development but is required for distinct memories in male, although not in female, mice. Mol. Cell. Biol. 26, 9094-9104
42. Morgado-Bernal, I. (2011) Learning and memory consolidation: linking molecular and behavioral data. Neuroscience 176, 12-19
43. Saneyoshi, T., Wayman, G., Fortin, D., Davare, M., Hoshi, N., Nozaki, N., Natsume, T., and Soderling, T. R. (2008) Activity-dependent synaptogenesis: regulation by a CaM kinase kinase/CaM kinase I/βPIX signaling complex. Neuron 57, 94-107
44. Hatten, M. E., and Heintz, N. (1995) Mechanisms of neural patterning and specification in the developing cerebellum. Annu. Rev. Neurosci. 18, 385-408
45. Wang, V. Y., and Zoghbi, H. Y. (2001) Genetic regulation of cerebellar development. Nat. Rev. Neurosci. 2, 484-491 (Pubitemid 33676583)
46. Sato, M., Suzuki, K., and Nakanishi, S. (2006) Expression profile of BDNF-responsive genes during cerebellar granule cell development. Biochem. Biophys. Res. Commun. 341, 304-309 (Pubitemid 43152106)
47. Morton, G. J., Cummings, D. E., Baskin, D. G., Barsh, G. S., and Schwartz, M. W. (2006) Central nervous system control of food intake and body weight. Nature 443, 289-295 (Pubitemid 44435142)
48. Williams, D. L., and Schwartz, M. W. (2011) Neuroanatomy of body weight control: lessons learned from leptin. J. Clin. Invest. 121, 2152-2155
49. Sainsbury, A., and Zhang, L. (2010) Role of the arcuate nucleus of the hypothalamus in regulation of body weight during energy deficit. Mol. Cell. Endocrinol. 316, 109-119
50. Lim, C. T., Kola, B., and Korbonits, M. (2011) The ghrelin/GOAT/GHS-R system and energy metabolism. Rev. Endocr. Metab. Disord. 12, 173-186
51. Kalra, S. P., and Kalra, P. S. (2004) NPY and cohorts in regulating appetite, obesity, and metabolic syndrome: beneficial effects of gene therapy. Neuropeptides 38, 201-211 (Pubitemid 39158859)
52. Andersson, U., Filipsson, K., Abbott, C. R., Woods, A., Smith, K., Bloom, S. R., Carling, D., and Small, C. J. (2004) AMP-activated protein kinase plays a role in the control of food intake. J. Biol. Chem. 279, 12005-12008 (Pubitemid 38445761)
53. 2+/calmodulin- dependent protein kinase kinases in the adult rat brain. Eur. J. Neurosci. 12, 89-99
54. Oury, F., Yadav, V. K., Wang, Y., Zhou, B., Liu, X. S., Guo, X. E., Tecott, L. H., Schutz, G., Means, A. R., and Karsenty, G. (2010) CREB mediates brain serotonin regulation of bone mass through its expression in ventromedial hypothalamic neurons. Genes Dev. 24, 2330-2342
55. Yadav, V. K., Oury, F., Suda, N., Liu, Z. W., Gao, X. B., Confavreux, C., Klemenhagen, K. C., Tanaka, K. F., Gingrich, J. A., Guo, X. E., Tecott, L. H., Mann, J. J., Hen, R., Horvath, T. L., and Karsenty, G. (2009) A serotonin-dependent mechanism explains the leptin regulation of bone mass, appetite, and energy expenditure. Cell 138, 976-989
56. Cristancho, A. G., and Lazar, M. A. (2011) Forming functional fat: a growing understanding of adipocyte differentiation. Nat. Rev. Mol. Cell Biol. 12, 722-734
57. McKinsey, T. A. (2007) Derepression of pathological cardiac genes by members of the CaM kinase superfamily. Cardiovasc. Res. 73, 667-677
58. Czubryt, M. P., McAnally, J., Fishman, G. I., and Olson, E. N. (2003) Regulation of peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α) and mitochondrial function by MEF2 and HDAC5. Proc. Natl. Acad. Sci. U.S.A. 100, 1711-1716 (Pubitemid 36254513)
59. He, L., Sabet, A., Djedjos, S., Miller, R., Sun, X., Hussain, M. A., Radovick, S., and Wondisford, F. E. (2009) Metformin and insulin suppress hepatic gluconeogenesis through phosphorylation of CREB-binding protein. Cell 137, 635-646
60. 2+/CaM-dependent protein kinase cascade in health and disease. Subcell. Biochem. 45, 169-214
61. Kitsos, C. M., Sankar, U., Illario, M., Colomer-Font, J. M., Duncan, A. W., Ribar, T. J., Reya, T., and Means, A. R. (2005) Calmodulin-dependent protein kinase IV regulates hematopoietic stem cell maintenance. J. Biol. Chem. 280, 33101-33108 (Pubitemid 41397105)
62. Nakaya, H. I., Wrammert, J., Lee, E. K., Racioppi, L., Marie-Kunze, S., Haining, W. N., Means, A. R., Kasturi, S. P., Khan, N., Li, G. M., McCausland, M., Kanchan, V., Kokko, K. E., Li, S., Elbein, R., Mehta, A. K., Aderem, A., Subbarao, K., Ahmed, R., and Pulendran, B. (2011) Systems biology of vaccination for seasonal influenza in humans. Nat. Immunol. 12, 786-795
63. Illario, M., Giardino-Torchia, M. L., Sankar, U., Ribar, T. J., Galgani, M., Vitiello, L., Masci, A. M., Bertani, F. R., Ciaglia, E., Astone, D., Maulucci, G., Cavallo, A., Vitale, M., Cimini, V., Pastore, L., Means, A. R., Rossi, G., and Racioppi, L. (2008) Calmodulin-dependent kinase IV links Toll-like receptor 4 signaling with survival pathway of activated dendritic cells. Blood 111, 723-731
64. Zhang, X., Guo, L., Collage, R. D., Stripay, J. L., Tsung, A., Lee, J. S., and Rosengart, M. R. (2011) Calcium/calmodulin-dependent protein kinase (CaMK) Iα mediates the macrophage inflammatory response to sepsis. J. Leukocyte. Biol. 90, 249-261
65. Salminen, A., Hyttinen, J. M., and Kaarniranta, K. (2011) AMP-activated protein kinase inhibits NFκB signaling and inflammation: impact on health span and life span. J. Mol. Med. 89, 667-676
66. Metcalf, D. (2007) Concise review: hematopoietic stem cells and tissue stem cells: current concepts and unanswered questions. Stem Cells 25, 2390-2395
67. Adams, G. B., Chabner, K. T., Alley, I. R., Olson, D. P., Szczepiorkowski, Z. M., Poznansky, M. C., Kos, C. H., Pollak, M. R., Brown, E. M., and Scadden, D. T. (2006) Stem cell engraftment at the endosteal niche is specified by the calcium-sensing receptor. Nature 439, 599-603 (Pubitemid 43185384)
68. Lam, B. S., Cunningham, C., and Adams, G. B. (2011) Pharmacologic modulation of the calcium-sensing receptor enhances hematopoietic stem cell lodgment in the adult bone marrow. Blood 117, 1167-1175
69. Laskin, D. L., Sunil, V. R., Gardner, C. R., and Laskin, J. D. (2011) Macrophages and tissue injury: agents of defense or destruction? Annu. Rev. Pharmacol. Toxicol. 51, 267-288
70. Olefsky, J. M., and Glass, C. K. (2010) Macrophages, inflammation, and insulin resistance. Annu. Rev. Physiol. 72, 219-246
71. Stearns-Kurosawa, D. J., Osuchowski, M. F., Valentine, C., Kurosawa, S., and Remick, D. G. (2011) The pathogenesis of sepsis. Annu. Rev. Pathol. 6, 19-48
72. Gutierrez-Ramos, J. C., and Bluethmann, H. (1997) Molecules and mechanisms operating in septic shock: lessons from knock-out mice. Immunol. Today 18, 329-334 (Pubitemid 27314469)
73. Lumeng, C. N., Maillard, I., and Saltiel, A. R. (2009) T-ing up inflammation in fat. Nat. Med. 15, 846-847
74. Lehrke, M., and Lazar, M. A. (2004) Inflamed about obesity. Nat. Med. 10, 126-127 (Pubitemid 38524875)
75. Yang, Z., Kahn, B. B., Shi, H., and Xue, B. Z. (2010) Macrophage α1 AMP-activated protein kinase (α1AMPK) antagonizes fatty acid-induced inflammation through SIRT1. J. Biol. Chem. 285, 19051-19059
76. Yuk, J. M., Shin, D. M., Lee, H. M., Kim, J. J., Kim, S. W., Jin, H. S., Yang, C. S., Park, K. A., Chanda, D., Kim, D. K., Huang, S. M., Lee, S. K., Lee, C. H., Kim, J. M., Song, C. H., Lee, S. Y., Hur, G. M., Moore, D. D., Choi, H. S., and Jo, E. K. (2011) The orphan nuclear receptor SHP acts as a negative regulator in inflammatory signaling triggered by Toll-like receptors. Nat. Immunol. 12, 742-751
77. Sag, D., Carling, D., Stout, R. D., and Suttles, J. (2008) Adenosine 5′-monophosphate-activated protein kinase promotes macrophage polarization to an anti-inflammatory functional phenotype. J. Immunol. 181, 8633-8641
78. Ryan, C. J., and Tindall, D. J. (2011) Androgen receptor rediscovered: the new biology and targeting the androgen receptor therapeutically. J. Clin. Oncol. 29, 3651-3658
79. Massie, C. E., Lynch, A., Ramos-Montoya, A., Boren, J., Stark, R., Fazli, L., Warren, A., Scott, H., Madhu, B., Sharma, N., Bon, H., Zecchini, V., Smith, D. M., Denicola, G. M., Mathews, N., Osborne, M., Hadfield, J., Macarthur, S., Adryan, B., Lyons, S. K., Brindle, K. M., Griffiths, J., Gleave, M. E., Rennie, P. S., Neal, D. E., and Mills, I. G. (2011) The androgen receptor fuels prostate cancer by regulating central metabolism and biosynthesis. EMBO J. 30, 2719-2733
80. Frigo, D. E., Howe, M. K., Wittmann, B. M., Brunner, A. M., Cushman, I., Wang, Q., Brown, M., Means, A. R., and McDonnell, D. P. (2011) CaM kinase kinase β-mediated activation of the growth regulatory kinase AMPK is required for androgen-dependent migration of prostate cancer cells. Cancer Res. 71, 528-537
81. Wayman, G. A., Tokumitsu, H., and Soderling, T. R. (1997) Inhibitory cross-talk by cAMP kinase on the calmodulin-dependent protein kinase cascade. J. Biol. Chem. 272, 16073-16076 (Pubitemid 27276416)
82. Park, S. J., Ahmad, F., Philp, A., Baar, K., Williams, T., Luo, H., Ke, H., Rehmann, H., Taussig, R., Brown, A. L., Kim, M. K., Beaven, M. A., Burgin, A. B., Manganiello, V., and Chung, J. H. (2012) Resveratrol ameliorates aging-related metabolic phenotypes by inhibiting cAMP phosphodiesterases. Cell 148, 421-433
83. 2+/ calmodulin-dependent protein kinase kinase. J. Biol. Chem. 277, 15813-15818