Abstract
Glycogen synthase kinase-3 (GSK-3) has attracted much scrutiny due to its plethora of cellular functions, novel mechanisms of regulation and its potential as a therapeutic target for several common diseases. In mammals, GSK-3 is encoded by two genes, termed GSK-3α and GSK-3β, that yield related but distinct protein-serine kinases. GSK-3 is unusual in that its protein kinase activity tends to be high in resting cells and cellular stimuli, such as hormones and growth factors, result in its catalytic inactivation. Further, many of the substrate proteins of GSK-3 are functionally inhibited by phosphorylation. Thus, signals that inhibit GSK-3 often cause activation of its diverse array of target proteins. Regulation of GSK-3 is important for normal development, regulation of metabolism, neuronal growth and differentiation and modulation of cell death. Dysregulation of GSK-3 activity has been implicated in human pathologies such as neurodegenerative diseases and type-2 diabetes. In this introductory chapter we provide a primer on the modes of GSK-3 regulation and a description of the various signaling pathways and cellular processes in which GSK-3 is an active participant.
Keywords: autophosphorylation, Wnt signaling, GSK-3 binding protein, Xenopus embryos, Hedgehog (Hh) ligand
Current Drug Targets
Title: Glycogen Synthase Kinase-3 - An Overview of An Over-Achieving Protein Kinase
Volume: 7 Issue: 11
Author(s): Lisa Kockeritz, Bradley Doble, Satish Patel and James R. Woodgett
Affiliation:
Keywords: autophosphorylation, Wnt signaling, GSK-3 binding protein, Xenopus embryos, Hedgehog (Hh) ligand
Abstract: Glycogen synthase kinase-3 (GSK-3) has attracted much scrutiny due to its plethora of cellular functions, novel mechanisms of regulation and its potential as a therapeutic target for several common diseases. In mammals, GSK-3 is encoded by two genes, termed GSK-3α and GSK-3β, that yield related but distinct protein-serine kinases. GSK-3 is unusual in that its protein kinase activity tends to be high in resting cells and cellular stimuli, such as hormones and growth factors, result in its catalytic inactivation. Further, many of the substrate proteins of GSK-3 are functionally inhibited by phosphorylation. Thus, signals that inhibit GSK-3 often cause activation of its diverse array of target proteins. Regulation of GSK-3 is important for normal development, regulation of metabolism, neuronal growth and differentiation and modulation of cell death. Dysregulation of GSK-3 activity has been implicated in human pathologies such as neurodegenerative diseases and type-2 diabetes. In this introductory chapter we provide a primer on the modes of GSK-3 regulation and a description of the various signaling pathways and cellular processes in which GSK-3 is an active participant.
Export Options
About this article
Cite this article as:
Kockeritz Lisa, Doble Bradley, Patel Satish and Woodgett R. James, Glycogen Synthase Kinase-3 - An Overview of An Over-Achieving Protein Kinase, Current Drug Targets 2006; 7 (11) . https://dx.doi.org/10.2174/1389450110607011377
DOI https://dx.doi.org/10.2174/1389450110607011377 |
Print ISSN 1389-4501 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5592 |
Call for Papers in Thematic Issues
New drug therapy for eye diseases
Eyesight is one of the most critical senses, accounting for over 80% of our perceptions. Our quality of life might be significantly affected by eye disease, including glaucoma, diabetic retinopathy, dry eye, etc. Although the development of microinvasive ocular surgery reduces surgical complications and improves overall outcomes, medication therapy is ...read more
RNA Molecules in the Treatment of Human Diseases
Messenger and non-coding RNAs, including long and small transcripts, are mediators of gene expression. Gene expression at the RNA level shows significant aberrations in human diseases, including cancer, leukemia, lymphoma, cardiovascular diseases, and neurological disorders. Human transcripts serve either as biomarkers of diagnosis, prognosis, prediction of treatment response and/or therapy ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
Related Articles
-
Is alpha-Synuclein Pathology a Target for Treatment of Neurodegenerative Disorders?
Current Alzheimer Research Synthetic Lethal Interactions in Cancer Therapy
Current Cancer Drug Targets Targeting IGF-I, IGFBPs and IGF-I Receptor System in Cancer: The Current and Future in Breast Cancer Therapy
Recent Patents on Anti-Cancer Drug Discovery CD248: Reviewing its Role in Health and Disease
Current Drug Targets Pathophysiological Implications of Dipeptidyl Peptidases
Current Protein & Peptide Science MicroRNA and Multiple Myeloma: from Laboratory Findings to Translational Therapeutic Approaches
Current Pharmaceutical Biotechnology Grape Seed Proanthocyanidins Protect N2a Cells against Ischemic Injury via Endoplasmic Reticulum Stress and Mitochondrial-associated Pathways
CNS & Neurological Disorders - Drug Targets Inhibition of Early Biochemical Defects in Prodromal Huntington’s disease by Simultaneous Activation of Nrf2 and Elevation of Multiple Micronutrients
Current Aging Science Nanotechnology Based Theranostic Approaches in Alzheimer's Disease Management: Current Status and Future Perspective
Current Alzheimer Research Alzheimers Disease: Interactions Between Cholinergic Functions and β- amyloid
Current Alzheimer Research Methylenetetrahydrofolate Reductase (MTHFR): A Novel Target for Cancer Therapy
Current Pharmaceutical Design Inhibitors of the TGF-β Superfamily and their Clinical Applications
Mini-Reviews in Medicinal Chemistry The Development of MetAP-2 Inhibitors in Cancer Treatment
Current Medicinal Chemistry Caffeine; the Forgotten Potential for Parkinson's Disease
CNS & Neurological Disorders - Drug Targets Tubulins as Therapeutic Targets in Cancer: from Bench to Bedside
Current Pharmaceutical Design The Ubiquitin-Proteasome System and Proteasome Inhibitors in Central Nervous System Diseases
Cardiovascular & Hematological Disorders-Drug Targets Protein Amyloidogenesis Investigated by Small Angle Scattering
Current Pharmaceutical Design The Urokinase Receptor Interactome
Current Pharmaceutical Design Amine Oxidase Inhibitors and Development of Neuroprotective Drugs
Current Neuropharmacology Targeting the PI3K/AKT/mTOR Signaling Pathway in Medulloblastoma
Current Molecular Medicine