GSK-3βまたはGSK3B: glycogen synthase kinase-3 beta)は、ヒトではGSK3B遺伝子にコードされる酵素プロテインキナーゼ)である[5][6]。GSK-3βの調節や発現の異常は、双極性障害の感受性の増大と関係している[7]

GSK3B
PDBに登録されている構造
PDBオルソログ検索: RCSB PDBe PDBj
PDBのIDコード一覧

1GNG, 1H8F, 1I09, 1J1B, 1J1C, 1O6K, 1O6L, 1O9U, 1PYX, 1Q3D, 1Q3W, 1Q41, 1Q4L, 1Q5K, 1R0E, 1UV5, 2JDO, 2JDR, 2JLD, 2O5K, 2OW3, 2UW9, 2X39, 2XH5, 3CQU, 3CQW, 3DU8, 3E87, 3E88, 3E8D, 3F7Z, 3F88, 3GB2, 3I4B, 3L1S, 3M1S, 3MV5, 3OW4, 3PUP, 3Q3B, 3QKK, 3SAY, 3SD0, 3ZDI, 3ZRK, 3ZRL, 3ZRM, 4ACC, 4ACD, 4ACG, 4ACH, 4AFJ, 4B7T, 4DIT, 4EKK, 4IQ6, 4J1R, 4J71, 4NM0, 4NM3, 4NM5, 4NM7, 4PTC, 4PTE, 4PTG, 5F94, 5F95, 5HLP, 5HLN

識別子
記号GSK3B, Gsk3b, 7330414F15Rik, 8430431H08Rik, C86142, GSK-3, GSK-3beta, GSK3, glycogen synthase kinase 3 beta
外部IDOMIM: 605004 MGI: 1861437 HomoloGene: 55629 GeneCards: GSK3B
EC番号2.7.11.1
遺伝子の位置 (ヒト)
3番染色体 (ヒト)
染色体3番染色体 (ヒト)[1]
3番染色体 (ヒト)
GSK3B遺伝子の位置
GSK3B遺伝子の位置
バンドデータ無し開始点119,821,321 bp[1]
終点120,094,994 bp[1]
遺伝子の位置 (マウス)
16番染色体 (マウス)
染色体16番染色体 (マウス)[2]
16番染色体 (マウス)
GSK3B遺伝子の位置
GSK3B遺伝子の位置
バンドデータ無し開始点37,909,363 bp[2]
終点38,066,446 bp[2]
RNA発現パターン
さらなる参照発現データ
遺伝子オントロジー
分子機能 キナーゼ活性
ATP binding
protein kinase activity
protein kinase A catalytic subunit binding
protein serine/threonine kinase activity
トランスフェラーゼ活性
NF-kappaB binding
tau-protein kinase activity
血漿タンパク結合
ヌクレオチド結合
p53結合
ubiquitin protein ligase binding
protease binding
beta-catenin binding
プロテインキナーゼ結合
dynactin binding
tau protein binding
細胞の構成要素 細胞質

ミトコンドリア
細胞核
中心体
細胞膜
細胞質基質
beta-catenin destruction complex
postsynapse
Wnt signalosome
核質
神経繊維
樹状突起
glutamatergic synapse
生物学的プロセス 周期的プロセス
negative regulation of type B pancreatic cell development
negative regulation of protein binding
negative regulation of glycogen (starch) synthase activity
glycogen metabolic process
上側頭回発生
negative regulation of canonical Wnt signaling pathway
chemical synaptic transmission, postsynaptic
negative regulation of protein-containing complex assembly
positive regulation of protein export from nucleus
positive regulation of GTPase activity
自己リン酸化
細胞分化
negative regulation of protein localization to nucleus
リン酸化
positive regulation of cell-matrix adhesion
神経系発生
dopamine receptor signaling pathway
上皮間葉転換
peptidyl-threonine phosphorylation
positive regulation of protein-containing complex assembly
positive regulation of neuron death
negative regulation of glycogen biosynthetic process
多細胞個体の発生
regulation of cellular response to heat
negative regulation of signal transduction
海馬発生
beta-catenin destruction complex disassembly
proteasome-mediated ubiquitin-dependent protein catabolic process
Wntシグナル経路
beta-catenin destruction complex assembly
タンパク質リン酸化
positive regulation of mitochondrion organization
intracellular signal transduction
positive regulation of protein catabolic process
negative regulation of dopaminergic neuron differentiation
ER overload response
概日リズム
peptidyl-serine phosphorylation
positive regulation of protein binding
positive regulation of proteasomal ubiquitin-dependent protein catabolic process
regulation of microtubule-based process
cellular response to interleukin-3
negative regulation of apoptotic process
canonical Wnt signaling pathway
extrinsic apoptotic signaling pathway in absence of ligand
positive regulation of mitochondrial outer membrane permeabilization involved in apoptotic signaling pathway
炭水化物代謝
neuron projection development
negative regulation of neuron death
positive regulation of gene expression
establishment of cell polarity
maintenance of cell polarity
regulation of axon extension
negative regulation of phosphoprotein phosphatase activity
regulation of dendrite morphogenesis
regulation of axonogenesis
興奮性シナプス後電位
regulation of microtubule cytoskeleton organization
negative regulation of calcineurin-NFAT signaling cascade
extrinsic apoptotic signaling pathway
neuron projection retraction
negative regulation of protein acetylation
cellular response to amyloid-beta
positive regulation of protein localization to centrosome
regulation of synaptic vesicle exocytosis
neuron projection organization
positive regulation of autophagy
regulation of circadian rhythm
regulation of long-term synaptic potentiation
regulation of microtubule anchoring at centrosome
出典:Amigo / QuickGO
オルソログ
ヒトマウス
Entrez
Ensembl
UniProt
RefSeq
(mRNA)

NM_001146156
NM_002093
NM_001354596

NM_019827
NM_001347232

RefSeq
(タンパク質)

NP_001139628
NP_002084
NP_001341525

NP_001334161
NP_062801

場所
(UCSC)
Chr 3: 119.82 – 120.09 MbChr 3: 37.91 – 38.07 Mb
PubMed検索[3][4]
ウィキデータ
閲覧/編集 ヒト閲覧/編集 マウス

機能

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GSK-3は、グリコーゲンシンターゼリン酸化して不活性化する因子として同定された、プロリン指向性セリン/スレオニンキナーゼである。2種類のアイソザイムGSK-3α英語版とGSK-3βのアミノ酸配列は高度な相同性を示す[5]。GSK-3βはエネルギー代謝、神経細胞の発生やパターン形成に関与している[8][9]

疾患との関係

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マウスでのGsk3b遺伝子座のホモ接合型破壊は、妊娠中期での致死となる[10]。この致死表現型は、TNFの阻害によってレスキューされる[10]

ヒトのGSK3B遺伝子の2つのSNP、rs334558(-50T/C)とrs3755557(-1727A/T)は、双極性障害におけるリチウム治療の有効性と関係している[11]

シグナル伝達経路

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結節性硬化症モデルでは、TSC2の喪失によって引き起こされたGSK-3βの活性やタンパク質合成の変化は、ERK1/2の薬理的阻害によって回復することが示されている[12]

相互作用

編集

GSK-3βは次に挙げる因子と相互作用することが示されている。

出典

編集
  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000082701 - Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000022812 - Ensembl, May 2017
  3. ^ Human PubMed Reference:
  4. ^ Mouse PubMed Reference:
  5. ^ a b “Mitogen inactivation of glycogen synthase kinase-3 beta in intact cells via serine 9 phosphorylation”. The Biochemical Journal 303 (Pt 3): 701–4. (November 1994). doi:10.1042/bj3030701. PMC 1137602. PMID 7980435. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1137602/. 
  6. ^ “Molecular cloning and characterization of the human glycogen synthase kinase-3beta promoter”. Genomics 60 (2): 121–8. (September 1999). doi:10.1006/geno.1999.5875. PMID 10486203. 
  7. ^ “The involvement of GSK3beta in bipolar disorder: integrating evidence from multiple types of genetic studies”. European Neuropsychopharmacology 20 (6): 357–68. (June 2010). doi:10.1016/j.euroneuro.2010.02.008. PMID 20226637. 
  8. ^ “Glycogen synthase kinase-3: functions in oncogenesis and development”. Biochimica et Biophysica Acta (BBA) - Reviews on Cancer 1114 (2–3): 147–62. (December 1992). doi:10.1016/0304-419X(92)90012-N. PMID 1333807. 
  9. ^ Entrez Gene: GSK3B glycogen synthase kinase 3 beta”. 2024年4月13日閲覧。
  10. ^ a b Hoeflich, K. P.; Luo, J.; Rubie, E. A.; Tsao, M. S.; Jin, O.; Woodgett, J. R. (2000-07-06). “Requirement for glycogen synthase kinase-3beta in cell survival and NF-kappaB activation”. Nature 406 (6791): 86–90. doi:10.1038/35017574. ISSN 0028-0836. PMID 10894547. https://pubmed.ncbi.nlm.nih.gov/10894547. 
  11. ^ “Haplotype analysis of GSK-3β gene polymorphisms in bipolar disorder lithium responders and nonresponders”. Clinical Neuropharmacology 37 (4): 108–10. (2013). doi:10.1097/WNF.0000000000000039. PMC 4206383. PMID 24992082. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4206383/. 
  12. ^ “Inhibition of ERK1/2 Restores GSK3β Activity and Protein Synthesis Levels in a Model of Tuberous Sclerosis”. Scientific Reports 7 (1): 4174. (June 2017). Bibcode2017NatSR...7.4174P. doi:10.1038/s41598-017-04528-5. PMC 5482840. PMID 28646232. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5482840/. 
  13. ^ a b “A-kinase anchoring protein AKAP220 binds to glycogen synthase kinase-3beta (GSK-3beta ) and mediates protein kinase A-dependent inhibition of GSK-3beta”. The Journal of Biological Chemistry 277 (40): 36955–61. (October 2002). doi:10.1074/jbc.M206210200. PMID 12147701. 
  14. ^ a b “The tuberin-hamartin complex negatively regulates beta-catenin signaling activity”. The Journal of Biological Chemistry 278 (8): 5947–51. (February 2003). doi:10.1074/jbc.C200473200. PMID 12511557. 
  15. ^ “Axin, an inhibitor of the Wnt signalling pathway, interacts with beta-catenin, GSK-3beta and APC and reduces the beta-catenin level”. Genes to Cells 3 (6): 395–403. (June 1998). doi:10.1046/j.1365-2443.1998.00198.x. PMID 9734785. 
  16. ^ “Hot spots in beta-catenin for interactions with LEF-1, conductin and APC”. Nature Structural Biology 7 (9): 800–7. (September 2000). doi:10.1038/79039. PMID 10966653. 
  17. ^ “The ankyrin repeat protein Diversin recruits Casein kinase Iepsilon to the beta-catenin degradation complex and acts in both canonical Wnt and Wnt/JNK signaling”. Genes & Development 16 (16): 2073–84. (August 2002). doi:10.1101/gad.230402. PMC 186448. PMID 12183362. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC186448/. 
  18. ^ “Suppression of androgen receptor-mediated transactivation and cell growth by the glycogen synthase kinase 3 beta in prostate cells”. The Journal of Biological Chemistry 279 (31): 32444–52. (July 2004). doi:10.1074/jbc.M313963200. PMID 15178691. 
  19. ^ “The interaction between beta-catenin, GSK3beta and APC after motogen induced cell-cell dissociation, and their involvement in signal transduction pathways in prostate cancer”. International Journal of Oncology 18 (4): 843–7. (April 2001). doi:10.3892/ijo.18.4.843. PMID 11251183. 
  20. ^ “DIX domains of Dvl and axin are necessary for protein interactions and their ability to regulate beta-catenin stability”. Molecular and Cellular Biology 19 (6): 4414–22. (June 1999). doi:10.1128/mcb.19.6.4414. PMC 104400. PMID 10330181. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC104400/. 
  21. ^ “Human dynamin-like protein interacts with the glycogen synthase kinase 3beta”. Biochemical and Biophysical Research Communications 249 (3): 697–703. (August 1998). doi:10.1006/bbrc.1998.9253. PMID 9731200. 
  22. ^ EMBL-EBI. “EMBL European Bioinformatics Institute” (英語). www.ebi.ac.uk.. 2017年4月26日閲覧。
  23. ^ “Skin stem cells orchestrate directional migration by regulating microtubule-ACF7 connections through GSK3β”. Cell 144 (3): 341–52. (February 2011). doi:10.1016/j.cell.2010.12.033. PMC 3050560. PMID 21295697. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3050560/. 
  24. ^ “Interaction of glycogen synthase kinase 3beta with the DF3/MUC1 carcinoma-associated antigen and beta-catenin”. Molecular and Cellular Biology 18 (12): 7216–24. (December 1998). doi:10.1128/mcb.18.12.7216. PMC 109303. PMID 9819408. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC109303/. 
  25. ^ “The c-Src tyrosine kinase regulates signaling of the human DF3/MUC1 carcinoma-associated antigen with GSK3 beta and beta-catenin”. The Journal of Biological Chemistry 276 (9): 6061–4. (March 2001). doi:10.1074/jbc.C000754200. PMID 11152665. 
  26. ^ “Axin and GSK3- control Smad3 protein stability and modulate TGF- signaling”. Genes & Development 22 (1): 106–20. (January 2008). doi:10.1101/gad.1590908. PMC 2151009. PMID 18172167. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2151009/. 
  27. ^ “Glycogen synthase kinase-3beta modulates notch signaling and stability”. Current Biology 12 (12): 1006–11. (June 2002). Bibcode2002CBio...12.1006F. doi:10.1016/S0960-9822(02)00888-6. PMID 12123574. 
  28. ^ “Phosphorylation by glycogen synthase kinase-3 beta down-regulates Notch activity, a link for Notch and Wnt pathways”. The Journal of Biological Chemistry 278 (34): 32227–35. (August 2003). doi:10.1074/jbc.M304001200. PMID 12794074. 
  29. ^ “Direct, activating interaction between glycogen synthase kinase-3beta and p53 after DNA damage”. Proceedings of the National Academy of Sciences of the United States of America 99 (12): 7951–5. (June 2002). Bibcode2002PNAS...99.7951W. doi:10.1073/pnas.122062299. PMC 123001. PMID 12048243. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC123001/. 
  30. ^ “Human serum and glucocorticoid-inducible kinase-like kinase (SGKL) phosphorylates glycogen syntheses kinase 3 beta (GSK-3beta) at serine-9 through direct interaction”. Biochemical and Biophysical Research Communications 293 (4): 1191–6. (May 2002). doi:10.1016/S0006-291X(02)00349-2. PMID 12054501. 
  31. ^ “TSC2 integrates Wnt and energy signals via a coordinated phosphorylation by AMPK and GSK3 to regulate cell growth”. Cell 126 (5): 955–68. (September 2006). doi:10.1016/j.cell.2006.06.055. PMID 16959574. 

関連文献

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関連項目

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外部リンク

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  • PDBe-KB provides an overview of all the structure information available in the PDB for Human Glycogen synthase kinase-3 beta (GSK3B)