GSK-3β
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.
関連文献
[編集]- “Glycogen synthase kinase3 beta phosphorylates serine 33 of p53 and activates p53's transcriptional activity”. BMC Cell Biology 2: 12. (2001). doi:10.1186/1471-2121-2-12. PMC 35361. PMID 11483158 .
- “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.
- “Hyperphosphorylation of tau in PHF”. Neurobiology of Aging 16 (3): 365–71; discussion 371–80. (1995). doi:10.1016/0197-4580(95)00027-C. PMID 7566346.
- “Mood stabilizers, glycogen synthase kinase-3beta and cell survival”. Molecular Psychiatry 7 (Suppl 1): S35-45. (2002). doi:10.1038/sj.mp.4001017. PMID 11986994.
- “GSK3beta signalling: casting a wide net in Alzheimer's disease”. Neuro-Signals 11 (5): 251–61. (2003). doi:10.1159/000067423. PMID 12566926.
- “GSK-3β inhibitor TWS119 attenuates rtPA-induced hemorrhagic transformation and activates the Wnt/β-catenin signaling pathway after acute ischemic stroke in rats”. Molecular Neurobiology 53 (10): 7028–7036. (December 2016). doi:10.1007/s12035-015-9607-2. PMC 4909586. PMID 26671619 .
- “[Schizophrenia, neurodevelopment and glycogen synthase kinase-3]”. Harefuah 142 (8–9): 636–42, 644. (September 2003). PMID 14518171.
- “PTEN and GSK3beta: key regulators of progression to androgen-independent prostate cancer”. Oncogene 25 (3): 329–37. (January 2006). doi:10.1038/sj.onc.1209020. PMID 16421604.
関連項目
[編集]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)