Deconstructing GSK-3: The Fine Regulation of Its Activity
- PMID: 21629747
- PMCID: PMC3100567
- DOI: 10.4061/2011/479249
Deconstructing GSK-3: The Fine Regulation of Its Activity
Abstract
Glycogen synthase kinase-3 (GSK-3) unique position in modulating the function of a diverse series of proteins in combination with its association with a wide variety of human disorders has attracted significant attention to the protein both as a therapeutic target and as a means to understand the molecular basis of these disorders. GSK-3 is ubiquitously expressed and, unusually, constitutively active in resting, unstimulated cells. In mammals, GSK-3α and β are each expressed widely at both the RNA and protein levels although some tissues show preferential levels of some of the two proteins. Neither gene appears to be acutely regulated at the transcriptional level, whereas the proteins are controlled posttranslationally, largely through protein-protein interactions or by posttranslational regulation. Control of GSK-3 activity thus occurs by complex mechanisms that are each dependent upon specific signalling pathways. Furthermore, GSK-3 appears to be a cellular nexus, integrating several signalling systems, including several second messengers and a wide selection of cellular stimulants. This paper will focus on the different ways to control GSK-3 activity (phosphorylation, protein complex formation, truncation, subcellular localization, etc.), the main signalling pathways involved in its control, and its pathological deregulation.
Similar articles
-
The mood stabilizing properties of AF3581, a novel potent GSK-3β inhibitor.Biomed Pharmacother. 2020 Aug;128:110249. doi: 10.1016/j.biopha.2020.110249. Epub 2020 May 26. Biomed Pharmacother. 2020. PMID: 32470749
-
New insights into the role of glycogen synthase kinase-3 in Alzheimer's disease.Expert Opin Ther Targets. 2014 Jan;18(1):69-77. doi: 10.1517/14728222.2013.843670. Epub 2013 Oct 8. Expert Opin Ther Targets. 2014. PMID: 24099155 Review.
-
Expression and regulation of glycogen synthase kinase 3 in human neutrophils.Int J Biochem Cell Biol. 2013 Nov;45(11):2660-5. doi: 10.1016/j.biocel.2013.09.001. Epub 2013 Sep 10. Int J Biochem Cell Biol. 2013. PMID: 24035907
-
Modulation of GSK-3 as a Therapeutic Strategy on Tau Pathologies.Front Mol Neurosci. 2011 Oct 5;4:24. doi: 10.3389/fnmol.2011.00024. eCollection 2011. Front Mol Neurosci. 2011. PMID: 22007157 Free PMC article.
-
Glycogen synthase kinase-3--an overview of an over-achieving protein kinase.Curr Drug Targets. 2006 Nov;7(11):1377-88. doi: 10.2174/1389450110607011377. Curr Drug Targets. 2006. PMID: 17100578 Review.
Cited by
-
EGCG inhibits the inflammation and senescence inducing properties of MDA-MB-231 triple-negative breast cancer (TNBC) cells-derived extracellular vesicles in human adipose-derived mesenchymal stem cells.Cancer Cell Int. 2023 Oct 13;23(1):240. doi: 10.1186/s12935-023-03087-2. Cancer Cell Int. 2023. PMID: 37833751 Free PMC article.
-
Regulation of Phosphorylation of Glycogen Synthase Kinase 3α and the Correlation with Sperm Motility in Human.World J Mens Health. 2024 Apr;42(2):373-383. doi: 10.5534/wjmh.230004. Epub 2023 Aug 9. World J Mens Health. 2024. PMID: 37635337 Free PMC article.
-
CMGC Kinases in Health and Cancer.Cancers (Basel). 2023 Jul 28;15(15):3838. doi: 10.3390/cancers15153838. Cancers (Basel). 2023. PMID: 37568654 Free PMC article. Review.
-
Untangling the Role of Tau in Huntington's Disease Pathology.J Huntingtons Dis. 2023;12(1):15-29. doi: 10.3233/JHD-220557. J Huntingtons Dis. 2023. PMID: 36806513 Free PMC article. Review.
-
HSD3B1 Expression Is Upregulated by Interleukin 4 in HT-29 Colon Cancer Cells via Multiple Signaling Pathways.Int J Mol Sci. 2022 Nov 5;23(21):13572. doi: 10.3390/ijms232113572. Int J Mol Sci. 2022. PMID: 36362361 Free PMC article.
References
-
- Rylatt DB, Aitken A, Bilham T, Condon GD, Embi N, Cohen P. Glycogen synthase from rabbit skeletal muscle. Amino acid sequence at the sites phosphorylated by glycogen synthase kinase-3, and extension of the N-terminal sequence containing the site phosphorylated by phosphorylase kinase. European Journal of Biochemistry. 1980;107(2):529–537. - PubMed
-
- Ferkey DM, Kimelman D. Glycogen synthase kinase-3β mutagenesis identifies a common binding domain for GBP and axin. Journal of Biological Chemistry. 2002;277(18):16147–16152. - PubMed
-
- Alessi DR, Caudwell FB, Andjelkovic M, Hemmings BA, Cohen P. Molecular basis for the substrate specificity of protein kinase B; comparison with MAPKAP kinase-1 and p70 S6 kinase. FEBS Letters. 1996;399(3):333–338. - PubMed
-
- Hanger DP, Hughes K, Woodgett JR, Brion JP, Anderton BH. Glycogen synthase kinase-3 induces Alzheimer’s disease-like phosphorylation of tau: generation of paired helical filament epitopes and neuronal localisation of the kinase. Neuroscience Letters. 1992;147(1):58–62. - PubMed
LinkOut - more resources
Full Text Sources
Other Literature Sources