CAMKK2: Difference between revisions
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{{ | '''Calcium/calmodulin-dependent protein kinase kinase 2''' is an [[enzyme]] that in humans is encoded by the ''CAMKK2'' [[gene]].<ref name="pmid9662074">{{cite journal | vauthors = Hsu LS, Tsou AP, Chi CW, Lee CH, Chen JY | title = Cloning, expression and chromosomal localization of human Ca<sup>2+</sup>/calmodulin-dependent protein kinase kinase | journal = J Biomed Sci | volume = 5 | issue = 2 | pages = 141–9 |date=Sep 1998 | pmid = 9662074 | pmc = | doi = 10.1159/000025324}}</ref><ref name=pmid9662074 /><ref name="entrez">{{cite web | title = Entrez Gene: CAMKK2 calcium/calmodulin-dependent protein kinase kinase 2, beta| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=10645| accessdate = }}</ref> | ||
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| | ==Function== | ||
| | The product of this gene belongs to the [[serine/threonine-specific protein kinase]] family, and to the Ca<sup>++</sup>/[[Ca2+/calmodulin-dependent protein kinase|calmodulin-dependent protein kinase]] subfamily. This protein plays a role in the calcium/calmodulin-dependent (CaM) kinase cascade by phosphorylating the downstream kinases [[CAMK1|CaMK1]] and [[CAMK4|CaMK4]].<ref name="entrez"/> | ||
| | |||
CaMKK2 regulates production of the appetite stimulating hormone [[neuropeptide Y]] and functions as an [[AMP-activated protein kinase|AMPK]] kinase in the [[hypothalamus]].<ref name="pmid18460329">{{cite journal | vauthors = Anderson KA, Ribar TJ, Lin F, Noeldner PK, Green MF, Muehlbauer MJ, Witters LA, Kemp BE, Means AR | title = Hypothalamic CaMKK2 contributes to the regulation of energy balance | journal = Cell Metab. | volume = 7 | issue = 5 | pages = 377–88 |date=May 2008 | pmid = 18460329 | doi = 10.1016/j.cmet.2008.02.011 | url = }}</ref> It also has an important role in the development of [[hyperalgesia]] and [[Drug tolerance|tolerance]] to [[opioid]] analgesic drugs, through reduction in downstream signalling pathways and [[mu opioid receptor]] downregulation.<ref name="pmid18006024">{{cite journal |vauthors=Sánchez-Blázquez P, Rodríguez-Muñoz M, Montero C, de la Torre-Madrid E, Garzón J |title=Calcium/calmodulin-dependent protein kinase II supports morphine antinociceptive tolerance by phosphorylation of glycosylated phosducin-like protein |journal=Neuropharmacology |volume=54 |issue=2 |pages=319–30 |date=February 2008 |pmid=18006024 |doi=10.1016/j.neuropharm.2007.10.002 |url=}}</ref><ref name="pmid18408996">{{cite journal |vauthors=Chen Y, Jiang Y, Yue W, Zhou Y, Lu L, Ma L |title=Chronic, but not acute morphine treatment, up-regulates alpha-Ca<sup>2+</sup>/calmodulin dependent protein kinase II gene expression in rat brain |journal=Neurochemical Research |volume=33 |issue=10 |pages=2092–8 |date=October 2008 |pmid=18408996 |doi=10.1007/s11064-008-9690-0 |url=}}</ref><ref name="pmid20053885">{{cite journal |vauthors=Chen Y, Yang C, Wang ZJ |title=Ca<sup>2+</sup>/calmodulin-dependent protein kinase II alpha is required for the initiation and maintenance of opioid-induced hyperalgesia |journal=Journal of Neuroscience |volume=30 |issue=1 |pages=38–46 |date=January 2010 |pmid=20053885 |doi=10.1523/JNEUROSCI.4346-09.2010 |url= |pmc=2821163}}</ref> Inhibition of CaMKK2 in mice reduces appetite and promotes weight loss.<ref name="pmid18460329"/> | |||
{{ | |||
==Isoforms== | |||
Seven transcript variants encoding six distinct isoforms have been identified for this gene. Additional splice variants have been described but their full-length nature has not been determined. The identified isoforms exhibit a distinct ability to undergo autophosphorylation and to phosphorylate the downstream kinases.<ref name="entrez"/><ref name="pmid11395482">{{cite journal | vauthors = Hsu LS, Chen GD, Lee LS, Chi CW, Cheng JF, Chen JY | title = Human Ca<sup>2+</sup>/calmodulin-dependent protein kinase kinase beta gene encodes multiple isoforms that display distinct kinase activity | journal = J. Biol. Chem. | volume = 276 | issue = 33 | pages = 31113–23 |date=August 2001 | pmid = 11395482 | doi = 10.1074/jbc.M011720200 | url = }}</ref> | |||
==References== | ==References== | ||
{{reflist| | {{reflist}} | ||
==External links== | |||
* {{UCSC gene info|CAMKK2}} | |||
==Further reading== | ==Further reading== | ||
{{refbegin | 2}} | {{refbegin | 2}} | ||
{{PBB_Further_reading | {{PBB_Further_reading | ||
| citations = | | citations = | ||
*{{cite journal | *{{cite journal | vauthors=Nakajima D, Okazaki N, Yamakawa H |title=Construction of expression-ready cDNA clones for KIAA genes: manual curation of 330 KIAA cDNA clones |journal=DNA Res. |volume=9 |issue= 3 |pages= 99–106 |year= 2003 |pmid= 12168954 |doi=10.1093/dnares/9.3.99 |display-authors=etal}} | ||
*{{cite journal | vauthors=Anderson KA, Means RL, Huang QH |title=Components of a calmodulin-dependent protein kinase cascade. Molecular cloning, functional characterization and cellular localization of Ca<sup>2+</sup>/calmodulin-dependent protein kinase kinase beta |journal=J. Biol. Chem. |volume=273 |issue= 48 |pages= 31880–9 |year= 1998 |pmid= 9822657 |doi=10.1074/jbc.273.48.31880 |display-authors=etal}} | |||
*{{cite journal | *{{cite journal | vauthors=Nagase T, Ishikawa K, Suyama M |title=Prediction of the coding sequences of unidentified human genes. XI. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro |journal=DNA Res. |volume=5 |issue= 5 |pages= 277–86 |year= 1999 |pmid= 9872452 |doi=10.1093/dnares/5.5.277 |display-authors=etal}} | ||
*{{cite journal | *{{cite journal | vauthors=Hsu LS, Chen GD, Lee LS |title=Human Ca<sup>2+</sup>/calmodulin-dependent protein kinase kinase beta gene encodes multiple isoforms that display distinct kinase activity |journal=J. Biol. Chem. |volume=276 |issue= 33 |pages= 31113–23 |year= 2001 |pmid= 11395482 |doi= 10.1074/jbc.M011720200 |display-authors=etal}} | ||
*{{cite journal | *{{cite journal | vauthors=Strausberg RL, Feingold EA, Grouse LH |title=Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=99 |issue= 26 |pages= 16899–903 |year= 2003 |pmid= 12477932 |doi= 10.1073/pnas.242603899 | pmc=139241 |display-authors=etal}} | ||
*{{cite journal | *{{cite journal | vauthors=Imai S, Okayama N, Shimizu M, Itoh M |title=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 |journal=Life Sci. |volume=72 |issue= 20 |pages= 2199–209 |year= 2003 |pmid= 12628440 |doi=10.1016/S0024-3205(03)00092-4 }} | ||
*{{cite journal | *{{cite journal | vauthors=Ishikawa Y, Tokumitsu H, Inuzuka H |title=Identification and characterization of novel components of a Ca<sup>2+</sup>/calmodulin-dependent protein kinase cascade in HeLa cells |journal=FEBS Lett. |volume=550 |issue= 1-3 |pages= 57–63 |year= 2003 |pmid= 12935886 |doi=10.1016/S0014-5793(03)00817-2 |display-authors=etal}} | ||
*{{cite journal | *{{cite journal | vauthors=Gerhard DS, Wagner L, Feingold EA |title=The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC) |journal=Genome Res. |volume=14 |issue= 10B |pages= 2121–7 |year= 2004 |pmid= 15489334 |doi= 10.1101/gr.2596504 | pmc=528928 |display-authors=etal}} | ||
*{{cite journal | *{{cite journal | vauthors=Hawley SA, Pan DA, Mustard KJ |title=Calmodulin-dependent protein kinase kinase-beta is an alternative upstream kinase for AMP-activated protein kinase |journal=Cell Metab. |volume=2 |issue= 1 |pages= 9–19 |year= 2005 |pmid= 16054095 |doi= 10.1016/j.cmet.2005.05.009 |display-authors=etal}} | ||
*{{cite journal | *{{cite journal | vauthors=Woods A, Dickerson K, Heath R |title=Ca<sup>2+</sup>/calmodulin-dependent protein kinase kinase-beta acts upstream of AMP-activated protein kinase in mammalian cells |journal=Cell Metab. |volume=2 |issue= 1 |pages= 21–33 |year= 2005 |pmid= 16054096 |doi= 10.1016/j.cmet.2005.06.005 |display-authors=etal}} | ||
*{{cite journal | *{{cite journal | vauthors=Novak G, Seeman P, Tallerico T |title=Increased expression of calcium/calmodulin-dependent protein kinase IIbeta in frontal cortex in schizophrenia and depression |journal=Synapse |volume=59 |issue= 1 |pages= 61–8 |year= 2006 |pmid= 16247765 |doi= 10.1002/syn.20211 }} | ||
*{{cite journal | *{{cite journal | vauthors=Stahmann N, Woods A, Carling D, Heller R |title=Thrombin activates AMP-activated protein kinase in endothelial cells via a pathway involving Ca<sup>2+</sup>/calmodulin-dependent protein kinase kinase beta |journal=Mol. Cell. Biol. |volume=26 |issue= 16 |pages= 5933–45 |year= 2006 |pmid= 16880506 |doi= 10.1128/MCB.00383-06 | pmc=1592798 }} | ||
*{{cite journal | *{{cite journal | vauthors=Erhardt A, Lucae S, Unschuld PG |title=Association of polymorphisms in P2RX7 and CaMKKb with anxiety disorders |journal=Journal of Affective Disorders |volume=101 |issue= 1-3 |pages= 159–68 |year= 2007 |pmid= 17197037 |doi= 10.1016/j.jad.2006.11.016 |display-authors=etal}} | ||
*{{cite journal | |||
}} | }} | ||
{{refend}} | {{refend}} | ||
{{ | {{NLM content}} | ||
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External IDs | GeneCards: [1] | ||||||
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Species | Human | Mouse | |||||
Entrez |
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Ensembl |
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UniProt |
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RefSeq (mRNA) |
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Location (UCSC) | n/a | n/a | |||||
PubMed search | n/a | n/a | |||||
Wikidata | |||||||
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Calcium/calmodulin-dependent protein kinase kinase 2 is an enzyme that in humans is encoded by the CAMKK2 gene.[1][1][2]
Function
The product of this gene belongs to the serine/threonine-specific protein kinase family, and to the Ca++/calmodulin-dependent protein kinase subfamily. This protein plays a role in the calcium/calmodulin-dependent (CaM) kinase cascade by phosphorylating the downstream kinases CaMK1 and CaMK4.[2]
CaMKK2 regulates production of the appetite stimulating hormone neuropeptide Y and functions as an AMPK kinase in the hypothalamus.[3] It also has an important role in the development of hyperalgesia and tolerance to opioid analgesic drugs, through reduction in downstream signalling pathways and mu opioid receptor downregulation.[4][5][6] Inhibition of CaMKK2 in mice reduces appetite and promotes weight loss.[3]
Isoforms
Seven transcript variants encoding six distinct isoforms have been identified for this gene. Additional splice variants have been described but their full-length nature has not been determined. The identified isoforms exhibit a distinct ability to undergo autophosphorylation and to phosphorylate the downstream kinases.[2][7]
References
- ↑ 1.0 1.1 Hsu LS, Tsou AP, Chi CW, Lee CH, Chen JY (Sep 1998). "Cloning, expression and chromosomal localization of human Ca2+/calmodulin-dependent protein kinase kinase". J Biomed Sci. 5 (2): 141–9. doi:10.1159/000025324. PMID 9662074.
- ↑ 2.0 2.1 2.2 "Entrez Gene: CAMKK2 calcium/calmodulin-dependent protein kinase kinase 2, beta".
- ↑ 3.0 3.1 Anderson KA, Ribar TJ, Lin F, Noeldner PK, Green MF, Muehlbauer MJ, Witters LA, Kemp BE, Means AR (May 2008). "Hypothalamic CaMKK2 contributes to the regulation of energy balance". Cell Metab. 7 (5): 377–88. doi:10.1016/j.cmet.2008.02.011. PMID 18460329.
- ↑ Sánchez-Blázquez P, Rodríguez-Muñoz M, Montero C, de la Torre-Madrid E, Garzón J (February 2008). "Calcium/calmodulin-dependent protein kinase II supports morphine antinociceptive tolerance by phosphorylation of glycosylated phosducin-like protein". Neuropharmacology. 54 (2): 319–30. doi:10.1016/j.neuropharm.2007.10.002. PMID 18006024.
- ↑ Chen Y, Jiang Y, Yue W, Zhou Y, Lu L, Ma L (October 2008). "Chronic, but not acute morphine treatment, up-regulates alpha-Ca2+/calmodulin dependent protein kinase II gene expression in rat brain". Neurochemical Research. 33 (10): 2092–8. doi:10.1007/s11064-008-9690-0. PMID 18408996.
- ↑ Chen Y, Yang C, Wang ZJ (January 2010). "Ca2+/calmodulin-dependent protein kinase II alpha is required for the initiation and maintenance of opioid-induced hyperalgesia". Journal of Neuroscience. 30 (1): 38–46. doi:10.1523/JNEUROSCI.4346-09.2010. PMC 2821163. PMID 20053885.
- ↑ Hsu LS, Chen GD, Lee LS, Chi CW, Cheng JF, Chen JY (August 2001). "Human Ca2+/calmodulin-dependent protein kinase kinase beta gene encodes multiple isoforms that display distinct kinase activity". J. Biol. Chem. 276 (33): 31113–23. doi:10.1074/jbc.M011720200. PMID 11395482.
External links
- Human CAMKK2 genome location and CAMKK2 gene details page in the UCSC Genome Browser.
Further reading
- Nakajima D, Okazaki N, Yamakawa H, et al. (2003). "Construction of expression-ready cDNA clones for KIAA genes: manual curation of 330 KIAA cDNA clones". DNA Res. 9 (3): 99–106. doi:10.1093/dnares/9.3.99. PMID 12168954.
- Anderson KA, Means RL, Huang QH, et al. (1998). "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. 273 (48): 31880–9. doi:10.1074/jbc.273.48.31880. PMID 9822657.
- Nagase T, Ishikawa K, Suyama M, et al. (1999). "Prediction of the coding sequences of unidentified human genes. XI. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro". DNA Res. 5 (5): 277–86. doi:10.1093/dnares/5.5.277. PMID 9872452.
- Hsu LS, Chen GD, Lee LS, et al. (2001). "Human Ca2+/calmodulin-dependent protein kinase kinase beta gene encodes multiple isoforms that display distinct kinase activity". J. Biol. Chem. 276 (33): 31113–23. doi:10.1074/jbc.M011720200. PMID 11395482.
- Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.
- Imai S, Okayama N, Shimizu M, Itoh M (2003). "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. 72 (20): 2199–209. doi:10.1016/S0024-3205(03)00092-4. PMID 12628440.
- Ishikawa Y, Tokumitsu H, Inuzuka H, et al. (2003). "Identification and characterization of novel components of a Ca2+/calmodulin-dependent protein kinase cascade in HeLa cells". FEBS Lett. 550 (1–3): 57–63. doi:10.1016/S0014-5793(03)00817-2. PMID 12935886.
- Gerhard DS, Wagner L, Feingold EA, et al. (2004). "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)". Genome Res. 14 (10B): 2121–7. doi:10.1101/gr.2596504. PMC 528928. PMID 15489334.
- Hawley SA, Pan DA, Mustard KJ, et al. (2005). "Calmodulin-dependent protein kinase kinase-beta is an alternative upstream kinase for AMP-activated protein kinase". Cell Metab. 2 (1): 9–19. doi:10.1016/j.cmet.2005.05.009. PMID 16054095.
- Woods A, Dickerson K, Heath R, et al. (2005). "Ca2+/calmodulin-dependent protein kinase kinase-beta acts upstream of AMP-activated protein kinase in mammalian cells". Cell Metab. 2 (1): 21–33. doi:10.1016/j.cmet.2005.06.005. PMID 16054096.
- Novak G, Seeman P, Tallerico T (2006). "Increased expression of calcium/calmodulin-dependent protein kinase IIbeta in frontal cortex in schizophrenia and depression". Synapse. 59 (1): 61–8. doi:10.1002/syn.20211. PMID 16247765.
- Stahmann N, Woods A, Carling D, Heller R (2006). "Thrombin activates AMP-activated protein kinase in endothelial cells via a pathway involving Ca2+/calmodulin-dependent protein kinase kinase beta". Mol. Cell. Biol. 26 (16): 5933–45. doi:10.1128/MCB.00383-06. PMC 1592798. PMID 16880506.
- Erhardt A, Lucae S, Unschuld PG, et al. (2007). "Association of polymorphisms in P2RX7 and CaMKKb with anxiety disorders". Journal of Affective Disorders. 101 (1–3): 159–68. doi:10.1016/j.jad.2006.11.016. PMID 17197037.
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