GSK-3: functional insights from cell biology and animal models
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 dive...
| Main Authors: | , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2011-11-01
|
| Series: | Frontiers in Molecular Neuroscience |
| Subjects: | |
| Online Access: | http://journal.frontiersin.org/Journal/10.3389/fnmol.2011.00040/full |
| _version_ | 1819295901487726592 |
|---|---|
| author | Oksana eKaidanovich-Beilin Jim Robert Woodgett |
| author_facet | Oksana eKaidanovich-Beilin Jim Robert Woodgett |
| author_sort | Oksana eKaidanovich-Beilin |
| collection | DOAJ |
| description | 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 knock-out 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. |
| first_indexed | 2024-12-24T04:49:35Z |
| format | Article |
| id | doaj.art-4040c230430644b1a694e169de70601f |
| institution | Directory Open Access Journal |
| issn | 1662-5099 |
| language | English |
| last_indexed | 2024-12-24T04:49:35Z |
| publishDate | 2011-11-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Molecular Neuroscience |
| spelling | doaj.art-4040c230430644b1a694e169de70601f2022-12-21T17:14:35ZengFrontiers Media S.A.Frontiers in Molecular Neuroscience1662-50992011-11-01410.3389/fnmol.2011.0004015384GSK-3: functional insights from cell biology and animal modelsOksana eKaidanovich-Beilin0Jim Robert Woodgett1Mount Sinai HospitalMount Sinai HospitalGlycogen 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 knock-out 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.http://journal.frontiersin.org/Journal/10.3389/fnmol.2011.00040/fullBehaviorBipolar DisorderLithiumSchizophreniaSignal Transductionanimal model |
| spellingShingle | Oksana eKaidanovich-Beilin Jim Robert Woodgett GSK-3: functional insights from cell biology and animal models Frontiers in Molecular Neuroscience Behavior Bipolar Disorder Lithium Schizophrenia Signal Transduction animal model |
| title | GSK-3: functional insights from cell biology and animal models |
| title_full | GSK-3: functional insights from cell biology and animal models |
| title_fullStr | GSK-3: functional insights from cell biology and animal models |
| title_full_unstemmed | GSK-3: functional insights from cell biology and animal models |
| title_short | GSK-3: functional insights from cell biology and animal models |
| title_sort | gsk 3 functional insights from cell biology and animal models |
| topic | Behavior Bipolar Disorder Lithium Schizophrenia Signal Transduction animal model |
| url | http://journal.frontiersin.org/Journal/10.3389/fnmol.2011.00040/full |
| work_keys_str_mv | AT oksanaekaidanovichbeilin gsk3functionalinsightsfromcellbiologyandanimalmodels AT jimrobertwoodgett gsk3functionalinsightsfromcellbiologyandanimalmodels |