Pharmacological inhibition of GSK-3 is not strictly correlated with a decrease in tyrosine phosphorylation of residues 216/279
- PMID: 17893926
- DOI: 10.1002/jnr.21523
Pharmacological inhibition of GSK-3 is not strictly correlated with a decrease in tyrosine phosphorylation of residues 216/279
Abstract
Recent evidence suggests that intramolecular autophosphorylation is responsible for the tyrosine phosphorylation (pY) of residues 279 or 216 of glycogen synthase kinase-3 (GSK-3alpha or beta), an event that appears to play an important role in regulating this kinase. This provocative hypothesis was based on the capacity of certain nonselective GSK-3 inhibitors to alter both the activity of GSK-3 and its pY. Inhibitors of GSK-3 are not always capable of preventing this tyrosine phosphorylation, which may require an extended period of time. For example, although lithium chloride inhibits GSK-3 activity, this inhibition does not alter its pY content. Furthermore, even when GSK-3 activity is impaired, GSK-3 pY can still be modified by physiological or pharmacological agents. Taken together, these data indicate that GSK-3 kinase activity is not necessarily correlated with the extent of GSK-3 pY. We hypothesized that some as-yet-unidentified tyrosine kinases and phosphatases may also regulate this kinase.
(c) 2007 Wiley-Liss, Inc.
Similar articles
-
Glycogen synthase kinase-3beta activity is required for androgen-stimulated gene expression in prostate cancer.Endocrinology. 2004 Jun;145(6):2941-9. doi: 10.1210/en.2003-1519. Epub 2004 Feb 26. Endocrinology. 2004. PMID: 14988390
-
Glycogen synthase kinase-3 regulates formation of long lamellipodia in human keratinocytes.J Cell Sci. 2003 Sep 15;116(Pt 18):3749-60. doi: 10.1242/jcs.00693. Epub 2003 Jul 30. J Cell Sci. 2003. PMID: 12890758
-
Glycogen synthase kinase-3beta is tyrosine-phosphorylated by MEK1 in human skin fibroblasts.Biochem Biophys Res Commun. 2004 Apr 2;316(2):411-5. doi: 10.1016/j.bbrc.2004.02.061. Biochem Biophys Res Commun. 2004. PMID: 15020233
-
Pharmacological inhibitors of glycogen synthase kinase 3.Trends Pharmacol Sci. 2004 Sep;25(9):471-80. doi: 10.1016/j.tips.2004.07.006. Trends Pharmacol Sci. 2004. PMID: 15559249 Review.
-
GSK-3 inhibition: achieving moderate efficacy with high selectivity.Biochim Biophys Acta. 2013 Jul;1834(7):1410-4. doi: 10.1016/j.bbapap.2013.01.016. Epub 2013 Jan 29. Biochim Biophys Acta. 2013. PMID: 23369789 Review.
Cited by
-
Substrate-selective positive allosteric modulation of PTPRD's phosphatase by flavonols.Biochem Pharmacol. 2022 Aug;202:115109. doi: 10.1016/j.bcp.2022.115109. Epub 2022 May 28. Biochem Pharmacol. 2022. PMID: 35636503 Free PMC article.
-
Glycogen synthase kinase-3β inhibitor SB216763 promotes DNA repair in ischemic retinal neurons.Neural Regen Res. 2021 Feb;16(2):394-400. doi: 10.4103/1673-5374.290913. Neural Regen Res. 2021. PMID: 32859805 Free PMC article.
-
The Presence of Seminal Plasma during Liquid Storage of Pig Spermatozoa at 17 °C Modulates Their Ability to Elicit In Vitro Capacitation and Trigger Acrosomal Exocytosis.Int J Mol Sci. 2020 Jun 25;21(12):4520. doi: 10.3390/ijms21124520. Int J Mol Sci. 2020. PMID: 32630462 Free PMC article.
-
Neuronal deletion of GSK3β increases microtubule speed in the growth cone and enhances axon regeneration via CRMP-2 and independently of MAP1B and CLASP2.BMC Biol. 2014 Jun 12;12:47. doi: 10.1186/1741-7007-12-47. BMC Biol. 2014. PMID: 24923837 Free PMC article.
-
Demonstrated brain insulin resistance in Alzheimer's disease patients is associated with IGF-1 resistance, IRS-1 dysregulation, and cognitive decline.J Clin Invest. 2012 Apr;122(4):1316-38. doi: 10.1172/JCI59903. J Clin Invest. 2012. PMID: 22476197 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources