GSK3B Antibodies
Background
GSK3B is a widely expressed serine/threonine protein kinase that exists in the cytoplasm and nucleus in a constitutive active form. This enzyme participates in regulating key biological processes such as glycogen metabolism, gene transcription, cell proliferation and differentiation by phosphorylating multiple substrates, especially playing a core regulatory role in multiple signaling pathways such as Wnt and Hedgehog. Initially discovered for its role in glycogen metabolism, subsequent studies have revealed that it is closely related to the pathological mechanisms of neurodegenerative diseases, diabetes and tumors. As a therapeutic target of lithium salts, the activity regulation mechanism of GSK3B provides an important direction for the development of related drugs, and its multi-level regulatory network remains an important model for the study of cell signal transduction to this day.
Structure of GSK3B
GSK3B is a serine/threonine protein kinase with a molecular weight of approximately 46 kDa. This protein has highly conserved catalytic domains among different species, and the differences in its molecular weight mainly result from sequence variations in the non-conserved regions.
| Species | Human | Mouse | Rat | Bovine | Zebrafish |
| Molecular Weight (kDa) | 46.7 | 47.1 | 46.9 | 46.5 | 47.3 |
| Primary Structural Differences | It has an N-terminal kinase domain and C-terminal extension | More than 95% homology with humans | Catalytic core highly conservative | Interspecific variations exist in the regulatory region | Retain core kinase function |
GSK3B is composed of 511 amino acids, and its three-dimensional structure shows a typical double-leafed kinase folding. The N-terminal lobe of this protein is mainly composed of β -folding to form an ATP-binding pocket, while the C-terminal lobe is mainly α -helical and participates in substrate recognition. A unique "fence-like" ring structure regulates substrate access to the catalytic center through steric hindrance mechanisms, and the phosphorylation of its N-terminal serine residue can induce conformational changes, forming a self-inhibitory state, which is a key structural feature for the regulation of kinase activity.
Fig. 1 Schematic of tau-GSK3b interaction in Alzheimer's disease and epilepsy.1
Key structural properties of GSK3B:
- Typical duplex kinase folding structure
- The N-terminal lobe β folds to form an ATP-binding pocket
- The α -helix of the C-terminal leaf forms the substrate recognition area
- The unique "fence-like" ring structure regulates substrate access
- N-terminal Ser9 phosphorylation sites mediated suppression conformation
Functions of GSK3B
As a multifunctional kinase, the core function of GSK3B lies in regulating cellular metabolism, signal transduction and gene expression through phosphorylation modification. This protein can not only promote cell differentiation and development under different physiological conditions, but also mediate stress responses and programmed death.
| Function | Description |
| Regulation of glycogen metabolism | Phosphorylates and inhibits the activity of glycogen synthase, directly regulating glycogen reserves in the liver and muscles. |
| Wnt signaling pathway | The β-catenin degrading complex is formed and the target protein is phosphorylated to be degraded by the proteasome. |
| Cell cycle regulation | Phosphorylated cyclin is involved in G2/M transition control and affects cell proliferation. |
| Apoptosis induction | Phosphorylating survival-promoting proteins under cellular stress conditions initiates the mitochondrial apoptotic pathway. |
| Neurodevelopmental support | Regulate the phosphorylation status of microtubule-binding proteins and maintain the polarity of neurons and axon orientation. |
The activity of GSK3B exhibits unique constitutive activation characteristics, and its regulation mainly relies on conformational autoinhibition induced by phosphorylation at the N-terminal Ser9 site. This dual state of "sustained activity - controlled inhibition" enables it to efficiently integrate multiple upstream signals such as insulin and Wnt, playing a core and pivotal role in metabolic homeostasis and cell fate determination.
Applications of GSK3B and GSK3B Antibody in Literature
1. Ryu, Hye Young, et al. "GSK3B induces autophagy by phosphorylating ULK1." Experimental & molecular medicine 53.3 (2021): 369-383. https://doi.org/10.1038/s12276-021-00570-6
The article indicates that under insulin deprivation conditions, GSK3B directly phosphorylates the S405 and S415 sites of ULK1, thereby enhancing the interaction between ULK1 and the autophagy-related protein MAP1LC3B/GABARAPL1 and promoting the occurrence of autophagy. This phosphorylation modification is significantly upregulated in human pancreatic cancer cells, suggesting that it may be involved in tumorigenesis.
2. Lv, Zhou, et al. "GSK3B Overexpression Alleviates Posttraumatic Osteoarthritis in Mice by Promoting DNMT1‐Mediated Hypermethylation of NR4A3 Promoter." Disease Markers 2022.1 (2022): 4185489. https://doi.org/10.1155/2022/4185489
Research has found that in traumatic osteoarthritis, GSK3B inhibits the expression of this inflammatory factor by recruiting the promoter regions of DNMT1 to NR4A3 genes and promoting their methylation. This mechanism blocks the activation of the NR4A3-mediated JAK2/STAT3 signaling pathway, ultimately alleviating the degeneration and apoptosis of chondrocytes.
3. Ogunleye, Adewale J., et al. "Molecular docking based screening analysis of GSK3B." Bioinformation 15.3 (2019): 201. https://doi.org/10.6026/97320630015201
In this study, through computational screening, it was found that compound BT-000775 is a highly selective GSK3B inhibitor. This compound has a strong binding force with GSK3B and excellent ADME properties, providing potential candidate drugs for the development of therapies targeting diseases related to its abnormal expression, such as specific subtypes of breast cancer.
4. Zheng, Yanhong, et al. "GSK3B inhibition reduced cervical cancer cell proliferation and migration by modulating the PI3K/Akt signaling pathway and epithelial-to-mesenchymal transition." Brazilian Journal of Medical and Biological Research 57 (2024): e13796. https://doi.org/10.1590/1414-431X2024e13796
This study reveals that GSK3B is highly expressed in cervical cancer and is associated with a poor prognosis. Inhibition of GSK3B can inhibit the proliferation, migration of HeLa cells and the growth of transplanted tumors by regulating the PI3K/Akt signaling pathway and the epithelial-mesenchymal transition process.
5. Toral-Rios, Danira, et al. "Synergistic Effect between the APOE ε4 Allele with Genetic Variants of GSK3B and MAPT: Differential Profile between Refractory Epilepsy and Alzheimer Disease." International Journal of Molecular Sciences 25.18 (2024): 10228. https://doi.org/10.3390/ijms251810228
This study found that in the Mexican population cohort, specific genetic variations of the GSK3B gene were associated with the risk of developing Alzheimer's disease and drug-resistant temporal lobe epilepsy. This risk is particularly significant when genetic interactions occur with the APOE ε4 allele.
Creative Biolabs: GSK3B Antibodies for Research
Creative Biolabs specializes in the production of high-quality GSK3B antibodies for research and industrial applications. Our portfolio includes monoclonal antibodies tailored for ELISA, Flow Cytometry, Western blot, immunohistochemistry, and other diagnostic methodologies.
- Custom GSK3B Antibody Development: Tailor-made solutions to meet specific research requirements.
- Bulk Production: Large-scale antibody manufacturing for industry partners.
- Technical Support: Expert consultation for protocol optimization and troubleshooting.
- Aliquoting Services: Conveniently sized aliquots for long-term storage and consistent experimental outcomes.
For more details on our GSK3B antibodies, custom preparations, or technical support, contact us at email.
Reference
- Toral-Rios, Danira, et al. "Synergistic Effect between the APOE ε4 Allele with Genetic Variants of GSK3B and MAPT: Differential Profile between Refractory Epilepsy and Alzheimer Disease." International Journal of Molecular Sciences 25.18 (2024): 10228. https://doi.org/10.3390/ijms251810228
Anti-GSK3B antibodies
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- AActivation
- AGAgonist
- APApoptosis
- BBlocking
- BABioassay
- BIBioimaging
- CImmunohistochemistry-Frozen Sections
- CIChromatin Immunoprecipitation
- CTCytotoxicity
- CSCostimulation
- DDepletion
- DBDot Blot
- EELISA
- ECELISA(Cap)
- EDELISA(Det)
- ESELISpot
- EMElectron Microscopy
- FFlow Cytometry
- FNFunction Assay
- GSGel Supershift
- IInhibition
- IAEnzyme Immunoassay
- ICImmunocytochemistry
- IDImmunodiffusion
- IEImmunoelectrophoresis
- IFImmunofluorescence
- IGImmunochromatography
- IHImmunohistochemistry
- IMImmunomicroscopy
- IOImmunoassay
- IPImmunoprecipitation
- ISIntracellular Staining for Flow Cytometry
- LALuminex Assay
- LFLateral Flow Immunoassay
- MMicroarray
- MCMass Cytometry/CyTOF
- MDMeDIP
- MSElectrophoretic Mobility Shift Assay
- NNeutralization
- PImmunohistologyp-Paraffin Sections
- PAPeptide Array
- PEPeptide ELISA
- PLProximity Ligation Assay
- RRadioimmunoassay
- SStimulation
- SESandwich ELISA
- SHIn situ hybridization
- TCTissue Culture
- WBWestern Blot



