CAMKK2: Difference between revisions
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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"/> |
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"/> |
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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 | author = 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 | year = 2008 | month = May | pmid = 18460329 | doi = 10.1016/j.cmet.2008.02.011 | url = }}</ref> Inhibition of CaMKK2 mice reduces appetite and promotes weight loss.<ref name="pmid18460329"/> |
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 | author = 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 | year = 2008 | month = May | pmid = 18460329 | doi = 10.1016/j.cmet.2008.02.011 | url = }}</ref> It also has an important role in the development of [[hyperalgesia]] and [[Pharmacological tolerance|tolerance]] to [[opioid]] analgesic drugs, through reduction in downstream signalling pathways and [[mu opioid receptor]] downregulation.<ref name="pmid18006024">{{cite journal |author=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 |year=2008 |month=February |pmid=18006024 |doi=10.1016/j.neuropharm.2007.10.002 |url=}}</ref><ref name="pmid18408996">{{cite journal |author=Chen Y, Jiang Y, Yue W, Zhou Y, Lu L, Ma L |title=Chronic, but not acute morphine treatment, up-regulates alpha-Ca2+/calmodulin dependent protein kinase II gene expression in rat brain |journal=Neurochemical Research |volume=33 |issue=10 |pages=2092–8 |year=2008 |month=October |pmid=18408996 |doi=10.1007/s11064-008-9690-0 |url=}}</ref><ref name="pmid20053885">{{cite journal |author=Chen Y, Yang C, Wang ZJ |title=Ca2+/calmodulin-dependent protein kinase II alpha is required for the initiation and maintenance of opioid-induced hyperalgesia |journal=The Journal of Neuroscience : the Official Journal of the Society for Neuroscience |volume=30 |issue=1 |pages=38–46 |year=2010 |month=January |pmid=20053885 |doi=10.1523/JNEUROSCI.4346-09.2010 |url=}}</ref> Inhibition of CaMKK2 mice reduces appetite and promotes weight loss.<ref name="pmid18460329"/> |
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==Isoforms== |
==Isoforms== |
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Revision as of 02:47, 21 April 2010
Template:PBB 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 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.[7][2]
References
- ^ a b Hsu LS, Tsou AP, Chi CW, Lee CH, Chen JY (1998). "Cloning, expression and chromosomal localization of human Ca2+/calmodulin-dependent protein kinase kinase". J Biomed Sci. 5 (2): 141–9. PMID 9662074.
{{cite journal}}: Unknown parameter|month=ignored (help)CS1 maint: multiple names: authors list (link) Cite error: The named reference "pmid9662074" was defined multiple times with different content (see the help page). - ^ a b c "Entrez Gene: CAMKK2 calcium/calmodulin-dependent protein kinase kinase 2, beta".
- ^ a b Anderson KA, Ribar TJ, Lin F, Noeldner PK, Green MF, Muehlbauer MJ, Witters LA, Kemp BE, Means AR (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.
{{cite journal}}: Unknown parameter|month=ignored (help)CS1 maint: multiple names: authors list (link) - ^ Sánchez-Blázquez P, Rodríguez-Muñoz M, Montero C, de la Torre-Madrid E, Garzón J (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.
{{cite journal}}: Unknown parameter|month=ignored (help)CS1 maint: multiple names: authors list (link) - ^ Chen Y, Jiang Y, Yue W, Zhou Y, Lu L, Ma L (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.
{{cite journal}}: Unknown parameter|month=ignored (help)CS1 maint: multiple names: authors list (link) - ^ Chen Y, Yang C, Wang ZJ (2010). "Ca2+/calmodulin-dependent protein kinase II alpha is required for the initiation and maintenance of opioid-induced hyperalgesia". The Journal of Neuroscience : the Official Journal of the Society for Neuroscience. 30 (1): 38–46. doi:10.1523/JNEUROSCI.4346-09.2010. PMID 20053885.
{{cite journal}}: Unknown parameter|month=ignored (help)CS1 maint: multiple names: authors list (link) - ^ Hsu LS, Chen GD, Lee LS, Chi CW, Cheng JF, Chen JY (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.
{{cite journal}}: Unknown parameter|month=ignored (help)CS1 maint: multiple names: authors list (link) CS1 maint: unflagged free DOI (link)
Further reading
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This article incorporates text from the United States National Library of Medicine, which is in the public domain.