Glycogen Synthase Kinase 3

Glycogen synthase kinase 3 (GSK-3), EC 2.7.11.26, is a serine-threonine kinase with two isoforms (α and β), that was originally discovered as an important enzyme in glycogen metabolism. GSK-3 was subsequently shown to function in cellular division, proliferation, motility and survival.

Products
Background
Literature (8)
Pathways (1)
Gene Data

Inhibitors

Cat. No. Product Name / Activity
4083 3F8
Potent and selective GSK-3β inhibitor
4431 A 1070722
Highly potent, selective GSK-3 inhibitor
6400 Alsterpaullone
GSK-3β inhibitor; also inhibits CDK1/2 and Lck
3966 AR-A 014418
Selective GSK-3 inhibitor
3194 BIO
Potent GSK-3 inhibitor; also inhibits cdks
3874 BIO-acetoxime
Selective GSK-3α/β inhibitor
6695 CHIR 98014
Highly potent and selective GSK-3 inhibitor
4423 CHIR 99021
Highly selective GSK-3 inhibitor
4953 CHIR 99021 trihydrochloride
Hydrochloride salt of CHIR 99021 (Cat. No. 4423); selective GSK-3 inhibitor
1813 Indirubin-3'-oxime
GSK-3β inhibitor; also inhibits cdks and other protein kinases
1398 Kenpaullone
GSK-3β inhibitor; also inhibits cdks
4740 Lithium carbonate
Mood stabilizer; inhibits GSK-3 in vivo
3873 MeBIO
Inactive analog of BIO (Cat. No. 3194)
1616 SB 216763
Potent, selective GSK-3 inhibitor
1617 SB 415286
Potent, selective GSK-3 inhibitor
4353 TC-G 24
Potent and selective GSK-3β inhibitor
3869 TCS 2002
Potent GSK-3β inhibitor
4221 TCS 21311
GSK-3β inhibitor. Also inhibits PKC and JAK3
6092 TDZD 8
Selective non-ATP competitive inhibitor of GSK 3β
3835 TWS 119
GSK-3β inhibitor; induces neuronal differentiation in ESCs

Substrates

Cat. No. Product Name / Activity
1802 2B-(SP)
Selective GSK-3 phosphopeptide substrate
1352 Phospho-Glycogen Synthase Peptide-2 (substrate)
GSK-3 substrate (synthetic)

Other

Cat. No. Product Name / Activity
2236 TCS 183
Fragment 1-13 of GSK-3β sequence
2320 TCS 184
Scrambled control peptide for use with TCS 183 (Cat. No. 2236)

The serine/threonine kinase Glycogen synthase kinase 3 (GSK-3) has two isoforms (α and β). GSK-3 is a key enzyme in glycogen metabolism, as well as cell division, proliferation, motility and survival. The enzyme plays a role in a number of pathological conditions, including cancer, diabetes and neurological diseases.

GSK-3 phosphorylates tau and presenilin-1, which are involved in the development of Alzheimer's disease. Both isoforms of GSK-3 are ubiquitously expressed, although particularly high levels of GSK-3β (also known as tau-protein kinase) are found in the brain, where it is involved in synaptic plasticity, possibly via regulation of NMDA receptor trafficking. GSK-3 phosphorylates over 40 different substrates including signaling proteins, transcription factors and structural proteins, and is part of the signal transduction cascade of a large number of growth factors and cytokines.

The activity of GSK is regulated by phosphorylation (Akt, S6K, RSK, PKA and PKC), dephosphorylation (PP1 and PP2A), and by binding to protein complexes. GSK-3β is a component of the canonical Wnt signaling pathway, forming part of a "destruction complex" with axin, APC, and casein kinase 1α (CK1α). In the absence of Wnt binding to its receptor, β-catenin the main signaling molecule in the Wnt pathway, binds axin and is phosphorylated by GSK-3β and CK1α. This tags β-catenin for ubiquitination and subsequent degradation by the proteasome, so maintaining low levels of β-catenin in the cytoplasm. Activation of Wnt receptors leads to inhibition of the destruction complex, including GSK-3β, resulting in accumulation of β-catenin, its translocation to the nucleus and the activation of transcription factors associated with pluripotency. Wnt signaling is important in stem cell differentiation and proliferation during embryogenesis as well as in adult tissues. It is also important in the development of the central nervous system and in the maintenance and repair of the adult brain.

GSK-3β is also important in the Hedgehog signaling pathway. Hedgehog proteins bind to a receptor known as Patched, which is internalized and degraded, releasing the G protein-coupled receptor Smoothened (SMO) to the membrane. This inhibits a complex consisting of protein kinase A (PKA), casein kinase 1 (CK1) and GSK-3β, and prevents phosphorylation of the suppressor of fused (SUFU)-glioma-associated oncogene homolog (GLI). This allows the dissociation of the SUFU-GLI complex, enabling translocation of the transcription factors GLI1 and GLI2 to the nucleus and activating transcription of Hh target genes. The Hedgehog pathway is important in embryonic development for the patterning of many tissues and organs. Hh signaling is also important in development of a range of cancers.

GSK-3 inhibitors are widely used in stem cell research for the differentiation and maintenance of cells.

External sources of pharmacological information for Glycogen Synthase Kinase 3 :

    Literature for Glycogen Synthase Kinase 3

    Tocris offers the following scientific literature for Glycogen Synthase Kinase 3 to showcase our products. We invite you to request* or download your copy today!

    *Please note that Tocris will only send literature to established scientific business / institute addresses.


    Cancer

    Cancer Research Product Guide

    A collection of over 750 products for cancer research, the guide includes research tools for the study of:

    • Cancer Metabolism
    • Epigenetics in Cancer
    • Receptor Signaling
    • Cell Cycle and DNA Damage Repair
    • Angiogenesis
    • Invasion and Metastasis
    Kinases

    Kinases Product Listing

    A collection of over 400 products for kinase research, the listing includes inhibitors of:

    • Receptor Tyrosine Kinases
    • Protein Kinases A, C, D and G
    • PI-3 Kinase, Akt and mTOR
    • MAPK Signaling
    • Receptor Serine/Threonine Kinases
    Neurodegeneration

    Neurodegeneration Product Guide

    A collection of over 275 products for neurodegeneration research, the guide includes research tools for the study of:

    • Alzheimer's disease
    • Parkinson's disease
    • Huntington's disease
    Stem Cell

    Stem Cell Research Product Guide

    This product guide provides a background to the use of small molecules in stem cell research and lists over 200 products for use in:

    • Self-renewal and Maintenance
    • Differentiation
    • Reprogramming
    • Organoid Generation
    • Regenerative Medicine
    Stem Cells

    Stem Cells Scientific Review

    Written by Kirsty E. Clarke, Victoria B. Christie, Andy Whiting and Stefan A. Przyborski, this review provides an overview of the use of small molecules in the control of stem cell growth and differentiation. Key signaling pathways are highlighted, and the regulation of ES cell self-renewal and somatic cell reprogramming is discussed. Compounds available from Tocris are listed.

    Alzheimer's

    Alzheimer's Poster

    Alzheimer's disease (AD) is a degenerative brain disease and the most common cause of dementia, affecting approximately 47 million people worldwide. Updated in 2015, this poster summarizes the structural and functional changes observed in the progression of this neurodegenerative disease, as well as classic AD drug targets.

    Schizophrenia

    Schizophrenia Poster

    Schizophrenia is a debilitating psychiatric disorder that affects 1% of the worldwide population. This poster describes the neurobiology of Schizophrenia, as well as highlighting the genetic and environmental factors that play a fundamental role in the etiology of the disease. The current and emerging drug targets are also discussed.

    Stem Cells

    Stem Cells Poster

    Written by Rebecca Quelch and Stefan Przyborski from Durham University (UK), this poster describes the isolation of pluripotent stem cells, their maintenance in culture, differentiation, and the generation and potential uses of organoids.

    Pathways for Glycogen Synthase Kinase 3

    Wnt

    Wnt Signaling Pathway

    The Wnt pathway is involved in cellular differentiation and proliferation in adult tissues and also during embryogenesis. Disturbances within the pathway may lead to the formation of tumors and promote metastasis.

    Glycogen Synthase Kinase 3 Gene Data

    Gene Species Gene Symbol Gene Accession No. Protein Accession No.
    GSK-3α Human GSK3A NM_019884 P49840
    Mouse Gsk3a NM_001031667 Q2NL51
    Rat Gsk3a NM_017344 P18265
    GSK-3β Human GSK3B NM_002093 P49841
    Mouse Gsk3b NM_019827 Q9WV60
    Rat Gsk3b NM_032080 P18266