Editing GSK-3 (section)

{{cs1 config|name-list-style=vanc}}
{{Short description|Class of enzymes}}
{{Infobox protein family
|Name=Glycogen synthase kinase 3, catalytic domain
|Symbol=STKc_GSK3 
|InterPro=IPR039192
|CDD=cd14137
}}
{{infobox protein
|Name= [[GSK3A|glycogen synthase kinase 3 alpha]]
|caption=
|image=
|width=
|HGNCid=4616
|Symbol=[[GSK3A]]
|AltSymbols=
|EntrezGene=2931
|OMIM=606784
|RefSeq=NM_019884
|UniProt=P49840
|PDB=
|ECnumber=2.7.11.26
|Chromosome=19
|Arm=q
|Band=13.2|LocusSupplementaryData=
}}
{{infobox protein
|Name=[[GSK3B|glycogen synthase kinase 3 beta]]
|image= 1J1B.png
|caption=[[X-ray crystallography#Biological macromolecular crystallography|Crystallographic structure]] of human GSK-3β (rainbow colored, [[N-terminus]] = blue, [[C-terminus]] = red) bound to phosphoaminophosphonic acid-adenylate ester (spheres).<ref name="pmid14993667">{{PDB|1J1B}}; {{cite journal | vauthors = Aoki M, Yokota T, Sugiura I, Sasaki C, Hasegawa T, Okumura C, Ishiguro K, Kohno T, Sugio S, Matsuzaki T | display-authors = 6 | title = Structural insight into nucleotide recognition in tau-protein kinase I/glycogen synthase kinase 3 beta | journal = Acta Crystallographica. Section D, Biological Crystallography | volume = 60 | issue = Pt 3 | pages = 439–446 | date = March 2004 | pmid = 14993667 | doi = 10.1107/S090744490302938X | bibcode = 2004AcCrD..60..439A }}</ref>
|width=
|HGNCid=4617
|Symbol=[[GSK3B]]
|AltSymbols=
|EntrezGene=2932
|OMIM=605004
|RefSeq=NM_002093
|UniProt=P49841
|PDB=1Q3W
|PDB_supplemental = [http://www.ebi.ac.uk/pdbe/searchResults.html?display=both&term=P49841 More structures]
|ECnumber=2.7.11.26
|Chromosome=3
|Arm=q
|Band=13.33
|LocusSupplementaryData=
}}
'''Glycogen synthase kinase 3''' ('''GSK-3''') is a [[serine/threonine protein kinase]] that mediates the addition of [[phosphate]] molecules onto [[serine]] and [[threonine]] amino acid residues. First discovered in 1980 as a regulatory kinase for its namesake, [[glycogen synthase]] (GS),<ref name="pmid6249596">{{cite journal | vauthors = Embi N, Rylatt DB, Cohen P | title = Glycogen synthase kinase-3 from rabbit skeletal muscle. Separation from cyclic-AMP-dependent protein kinase and phosphorylase kinase | journal = European Journal of Biochemistry | volume = 107 | issue = 2 | pages = 519–527 | date = June 1980 | pmid = 6249596 | doi = 10.1111/j.1432-1033.1980.tb06059.x | doi-access = free }}</ref> GSK-3 has since been identified as a [[protein kinase]] for over 100 different proteins in a variety of different pathways.<ref name="pmid25435019 ">{{cite journal | vauthors = Beurel E, Grieco SF, Jope RS | title = Glycogen synthase kinase-3 (GSK3): regulation, actions, and diseases | journal = Pharmacology & Therapeutics | volume = 148 | pages = 114–131 | date = April 2015 | pmid = 25435019 | pmc = 4340754 | doi = 10.1016/j.pharmthera.2014.11.016 }}</ref><ref name="pmid15102436">{{cite journal | vauthors = Jope RS, Johnson GV | title = The glamour and gloom of glycogen synthase kinase-3 | journal = Trends in Biochemical Sciences | volume = 29 | issue = 2 | pages = 95–102 | date = February 2004 | pmid = 15102436 | doi = 10.1016/j.tibs.2003.12.004 }}</ref> In mammals, including humans, GSK-3 exists in two [[isozyme]]s encoded by two [[Homology (biology)|homologous]] genes GSK-3α ([[GSK3A]]) and GSK-3β ([[GSK3B]]). GSK-3 has been the subject of much research since it has been implicated in a number of diseases, including [[type 2 diabetes]], [[Alzheimer's disease]], [[inflammation]], [[cancer]], [[addiction]]<ref>{{Cite journal | vauthors = Turlik J, Wąsikiewicz E, Domaradzka A, Chrostek G, Gniadzik W, Domagalski M, Duda P |date=December 2021 |title=GSK3β Activity in Reward Circuit Functioning and Addiction |journal=NeuroSci |language=en |volume=2 |issue=4 |pages=443–466 |doi=10.3390/neurosci2040033 |issn=2673-4087|doi-access=free }}</ref> and [[bipolar disorder]].

GSK-3 is a serine/threonine protein kinase that [[phosphorylate]] either [[threonine]] or [[serine]], and this phosphorylation controls a variety of biological activities, such as [[glycogen]] metabolism, [[cell signaling]], [[cellular transport]], and others.<ref>{{cite journal | vauthors = Pandey MK, DeGrado TR | title = Glycogen Synthase Kinase-3 (GSK-3)-Targeted Therapy and Imaging | journal = Theranostics | volume = 6 | issue = 4 | pages = 571–593 | year = 2016 | pmid = 26941849 | pmc = 4775866 | doi = 10.7150/thno.14334 }}</ref> GS inhibition by GSK-3β leads to a decrease in glycogen synthesis in the liver and muscles, along with increased blood glucose or hyperglycemia.<ref>{{cite journal | vauthors = Ali A, Hoeflich KP, Woodgett JR | title = Glycogen synthase kinase-3: properties, functions, and regulation | journal = Chemical Reviews | volume = 101 | issue = 8 | pages = 2527–2540 | date = August 2001 | pmid = 11749387 | doi = 10.1021/cr000110o }}</ref> This is why GSK-3β is associated with the pathogenesis and progression of many diseases, such as [[diabetes]], [[obesity]], [[cancer]],<ref>{{cite journal | vauthors = Eldar-Finkelman H | title = Glycogen synthase kinase 3: an emerging therapeutic target | journal = Trends in Molecular Medicine | volume = 8 | issue = 3 | pages = 126–132 | date = March 2002 | pmid = 11879773 | doi = 10.1016/S1471-4914(01)02266-3 }}</ref> and Alzheimer's disease.<ref name="pmid18088381">{{cite journal | vauthors = Hooper C, Killick R, Lovestone S | title = The GSK3 hypothesis of Alzheimer's disease | journal = Journal of Neurochemistry | volume = 104 | issue = 6 | pages = 1433–1439 | date = March 2008 | pmid = 18088381 | pmc = 3073119 | doi = 10.1111/j.1471-4159.2007.05194.x }}</ref> It is active in resting cells and is inhibited by several hormones such as [[insulin]], [[endothelial growth factor]], and [[platelet-derived growth factor]]. Insulin indirectly inactivates GSK3 via downstream phosphorylation of the specific serine residues Ser21 and Ser9 in GSK-3 isoforms α and β, respectively via the [[PI3K/Akt pathway]].<ref name="hermida-kumar-2017">{{cite journal |last1=Hermida |first1=Miguel A. |last2=Kumar |first2=J. Dinesh |last3=Leslie |first3=Nick R. |title=GSK3 and its interactions with the PI3K/AKT/mTOR signalling network |journal=Advances in Biological Regulation |date=August 2017 |volume=65 |pages=5–15 |doi=10.1016/j.jbior.2017.06.003 |pmid=28712664 |url=https://pubmed.ncbi.nlm.nih.gov/28712664/ |access-date=15 December 2023}}</ref><ref name="insulin-akt-pp1-2019">{{cite journal |last1=Li |first1=Qiqi |last2=Zhao |first2=Qiuye |last3=Zhang |first3=Junyu |last4=Linkang |first4=Linkang |last5=Wenhao |first5=Wenhao |last6=Chua |first6=BoonTin |last7=Chen |first7=Yan |last8=Xu |first8=Li |last9=Li |first9=Peng |title=The Protein Phosphatase 1 Complex Is a Direct Target of AKT that Links Insulin Signaling to Hepatic Glycogen Deposition |journal=Cell Reports |date=September 24, 2019|volume=28 |issue=13 |pages=3406–3422 |doi=10.1016/j.celrep.2019.08.066 |pmid=31553910 |doi-access=free }}</ref>

{{As of|2019}}, GSK-3 is the only type of '''glycogen synthase kinase''' named and recognized. The [[gene symbol]]s for GSK1 and GSK2 have been withdrawn by the [[HUGO Gene Nomenclature Committee]] (HGNC), and no new names for these "genes" nor their locations have been specified.<ref>{{MeshName|Glycogen+synthase+kinase}}</ref><ref>[https://www.ncbi.nlm.nih.gov/gene/2929 GSK1], [https://www.ncbi.nlm.nih.gov/gene/2930 GSK2]. ''NCBI Gene''.</ref>