| GSK-3: Functional Insights from Cell Biology and Animal Models. | |
| | |
MedLine Citation:
|
PMID: 22110425 Owner: NLM Status: PubMed-not-MEDLINE |
Abstract/OtherAbstract:
|
Glycogen synthase kinase-3 (GSK-3) is a widely expressed and highly conserved serine/threonine protein kinase encoded in mammals by two genes that generate two related proteins: GSK-3α and GSK-3β. GSK-3 is active in cells under resting conditions and is primarily regulated through inhibition or diversion of its activity. While GSK-3 is one of the few protein kinases that can be inactivated by phosphorylation, the mechanisms of GSK-3 regulation are more varied and not fully understood. Precise control appears to be achieved by a combination of phosphorylation, localization, and sequestration by a number of GSK-3-binding proteins. GSK-3 lies downstream of several major signaling pathways including the phosphatidylinositol 3' kinase pathway, the Wnt pathway, Hedgehog signaling and Notch. Specific pools of GSK-3, which differ in intracellular localization, binding partner affinity, and relative amount are differentially sensitized to several distinct signaling pathways and these sequestration mechanisms contribute to pathway insulation and signal specificity. Dysregulation of signaling pathways involving GSK-3 is associated with the pathogenesis of numerous neurological and psychiatric disorders and there are data suggesting GSK-3 isoform-selective roles in several of these. Here, we review the current knowledge of GSK-3 regulation and targets and discuss the various animal models that have been employed to dissect the functions of GSK-3 in brain development and function through the use of conventional or conditional knockout mice as well as transgenic mice. These studies have revealed fundamental roles for these protein kinases in memory, behavior, and neuronal fate determination and provide insights into possible therapeutic interventions. |
| | |
Authors:
|
Oksana Kaidanovich-Beilin; James Robert Woodgett |
Related Documents
:
|
21920725 - The regulation of tnf signalling: what a tangled web we weave. 15236585 - Phosphorylation and binding interactions of chey studied by use of badan-labeled protein. 9535095 - Chemotactic response regulator mutant chey95iv exhibits enhanced binding to the flagell... 12007495 - Analysis of protein phosphorylation using mass spectrometry: deciphering the phosphopro... 9625745 - Nuclear import of protein kinase c occurs by a mechanism distinct from the mechanism us... 3126065 - Synergistic stimulation of s-adenosylmethionine decarboxylase activity by ca2+ ionophor... |
Publication Detail:
|
Type: Journal Article Date: 2011-11-16 |
Journal Detail:
|
Title: Frontiers in molecular neuroscience Volume: 4 ISSN: 1662-5099 ISO Abbreviation: Front Mol Neurosci Publication Date: 2011 |
Date Detail:
|
Created Date: 2011-11-23 Completed Date: 2011-11-23 Revised Date: 2011-12-13 |
Medline Journal Info:
|
Nlm Unique ID: 101477914 Medline TA: Front Mol Neurosci Country: Switzerland |
Other Details:
|
Languages: eng Pagination: 40 Citation Subset: - |
Affiliation:
|
Samuel Lunenfeld Research Institute, Mount Sinai Hospital Toronto, ON, Canada. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
|
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Age Differences in Striatal Delay Sensitivity during Intertemporal Choice in Healthy Adults.
Next Document: GSK-3 Mouse Models to Study Neuronal Apoptosis and Neurodegeneration.