GSK-3β

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ID	OMIM: 605004 MGI: 1861437 HomoloGene: 55629 GeneCards: GSK3B
EC番号	2.7.11.1
遺伝子の位置 (ヒト)
染色体	3番染色体 (ヒト)
終点	120,094,994 bp
遺伝子の位置 (マウス)
染色体	16番染色体 (マウス)
終点	38,066,446 bp
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; • 膜; • 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
	2932
	56637
	ENSG00000082701
	ENSMUSG00000022812
	P49841
	Q9WV60
	NM_001146156; NM_002093; NM_001354596
	NM_019827; NM_001347232
	NP_001139628; NP_002084; NP_001341525
	NP_001334161; NP_062801
	ウィキデータ
閲覧/編集ヒト	閲覧/編集マウス

GSK-3βまたはGSK3B（英: 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]。

機能[編集]

GSK-3は、グリコーゲンシンターゼを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[編集]

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[編集]

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]

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000082701 - Ensembl, May 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000022812 - Ensembl, May 2017
^ Human PubMed Reference:
^ Mouse PubMed Reference:
^ ^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.
^ “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.
^ “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.
^ “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.
^ “Entrez Gene: GSK3B glycogen synthase kinase 3 beta”. 2024年4月13日閲覧。
^ ^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.
^ “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.
^ “Inhibition of ERK1/2 Restores GSK3β Activity and Protein Synthesis Levels in a Model of Tuberous Sclerosis”. Scientific Reports 7 (1): 4174. (June 2017). Bibcode: 2017NatSR...7.4174P. doi:10.1038/s41598-017-04528-5. PMC 5482840. PMID 28646232.
^ ^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.
^ ^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.
^ “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.
^ “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.
^ “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.
^ “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.
^ “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.
^ “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.
^ “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.
^ EMBL-EBI. “EMBL European Bioinformatics Institute” (英語). www.ebi.ac.uk.. 2017年4月26日閲覧。
^ “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.
^ “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.
^ “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.
^ “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.
^ “Glycogen synthase kinase-3beta modulates notch signaling and stability”. Current Biology 12 (12): 1006–11. (June 2002). Bibcode: 2002CBio...12.1006F. doi:10.1016/S0960-9822(02)00888-6. PMID 12123574.
^ “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.
^ “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). Bibcode: 2002PNAS...99.7951W. doi:10.1073/pnas.122062299. PMC 123001. PMID 12048243.
^ “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.
^ “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.

外部リンク[編集]

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

[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000082701 - Ensembl, May 2017

[refGRCm38Ensembl-2] GRCm38: Ensembl release 89: ENSMUSG00000022812 - Ensembl, May 2017

[3] Human PubMed Reference:

[4] Mouse PubMed Reference:

[pmid7980435-5] “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.

[pmid10486203-6] “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.

[:0-7] “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.

[pmid1333807-8] “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.

[:1-9] “Entrez Gene: GSK3B glycogen synthase kinase 3 beta”. 2024年4月13日閲覧。

[:2-10] 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.

[:3-11] “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.

[pmid28646232-12] “Inhibition of ERK1/2 Restores GSK3β Activity and Protein Synthesis Levels in a Model of Tuberous Sclerosis”. Scientific Reports 7 (1): 4174. (June 2017). Bibcode: 2017NatSR...7.4174P. doi:10.1038/s41598-017-04528-5. PMC 5482840. PMID 28646232.

[pmid12147701-13] “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.

[pmid12511557-14] “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.

[pmid9734785-15] “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.

[pmid10966653-16] “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.

[pmid12183362-17] “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.

[pmid15178691-18] “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.

[pmid11251183-19] “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.

[pmid10330181-20] “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.

[pmid9731200-21] “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.

[pmid9819408-24] “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.

[pmid11152665-25] “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.

[pmid18172167-26] “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.

[pmid12123574-27] “Glycogen synthase kinase-3beta modulates notch signaling and stability”. Current Biology 12 (12): 1006–11. (June 2002). Bibcode: 2002CBio...12.1006F. doi:10.1016/S0960-9822(02)00888-6. PMID 12123574.

[pmid12794074-28] “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.

[pmid12048243-29] “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). Bibcode: 2002PNAS...99.7951W. doi:10.1073/pnas.122062299. PMC 123001. PMID 12048243.

[pmid12054501-30] “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.

[pmid16959574-31] “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.

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