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Mouse Anti-GSK3B Recombinant Antibody (CBLG1-1878) (CBMAB-G5242-LY)

This product is antibody recognizes GSK3B. The antibody CBLG1-1878 immunoassay techniques such as: WB.
See all GSK3B antibodies

Summary

Host Animal
Mouse
Specificity
Human, Mouse, Rat
Clone
CBLG1-1878
Antibody Isotype
IgG
Application
WB

Basic Information

Immunogen
Recombinant Protein
Specificity
Human, Mouse, Rat
Antibody Isotype
IgG
Clonality
Monoclonal
Application Notes
The COA includes recommended starting dilutions, optimal dilutions should be determined by the end user.

Formulations & Storage [For reference only, actual COA shall prevail!]

Format
Liquid
Purity
> 95% Purity determined by SDS-PAGE.
Storage
Store at +4°C short term (1-2 weeks). Aliquot and store at -20°C long term. Avoid repeated freezethaw cycles.

Target

Full Name
Glycogen Synthase Kinase 3 Beta
Introduction
The protein encoded by this gene is a serine-threonine kinase belonging to the glycogen synthase kinase subfamily. It is a negative regulator of glucose homeostasis and is involved in energy metabolism, inflammation, ER-stress, mitochondrial dysfunction, and apoptotic pathways. Defects in this gene have been associated with Parkinson disease and Alzheimer disease. [provided by RefSeq, Aug 2017]
Entrez Gene ID
Human2932
Mouse56637
Rat84027
UniProt ID
HumanP49841
MouseQ9WV60
RatP18266
Function
Constitutively active protein kinase that acts as a negative regulator in the hormonal control of glucose homeostasis, Wnt signaling and regulation of transcription factors and microtubules, by phosphorylating and inactivating glycogen synthase (GYS1 or GYS2), EIF2B, CTNNB1/beta-catenin, APC, AXIN1, DPYSL2/CRMP2, JUN, NFATC1/NFATC, MAPT/TAU and MACF1 (PubMed:1846781, PubMed:9072970, PubMed:14690523, PubMed:20937854, PubMed:12554650, PubMed:11430833, PubMed:16484495).

Requires primed phosphorylation of the majority of its substrates (PubMed:11430833, PubMed:16484495).

In skeletal muscle, contributes to insulin regulation of glycogen synthesis by phosphorylating and inhibiting GYS1 activity and hence glycogen synthesis (PubMed:8397507).

May also mediate the development of insulin resistance by regulating activation of transcription factors (PubMed:8397507).

Regulates protein synthesis by controlling the activity of initiation factor 2B (EIF2BE/EIF2B5) in the same manner as glycogen synthase (PubMed:8397507).

In Wnt signaling, GSK3B forms a multimeric complex with APC, AXIN1 and CTNNB1/beta-catenin and phosphorylates the N-terminus of CTNNB1 leading to its degradation mediated by ubiquitin/proteasomes (PubMed:12554650).

Phosphorylates JUN at sites proximal to its DNA-binding domain, thereby reducing its affinity for DNA (PubMed:1846781).

Phosphorylates NFATC1/NFATC on conserved serine residues promoting NFATC1/NFATC nuclear export, shutting off NFATC1/NFATC gene regulation, and thereby opposing the action of calcineurin (PubMed:9072970).

Phosphorylates MAPT/TAU on 'Thr-548', decreasing significantly MAPT/TAU ability to bind and stabilize microtubules (PubMed:14690523).

MAPT/TAU is the principal component of neurofibrillary tangles in Alzheimer disease (PubMed:14690523).

Plays an important role in ERBB2-dependent stabilization of microtubules at the cell cortex (PubMed:20937854).

Phosphorylates MACF1, inhibiting its binding to microtubules which is critical for its role in bulge stem cell migration and skin wound repair (By similarity).

Probably regulates NF-kappa-B (NFKB1) at the transcriptional level and is required for the NF-kappa-B-mediated anti-apoptotic response to TNF-alpha (TNF/TNFA) (By similarity).

Negatively regulates replication in pancreatic beta-cells, resulting in apoptosis, loss of beta-cells and diabetes (By similarity).

Through phosphorylation of the anti-apoptotic protein MCL1, may control cell apoptosis in response to growth factors deprivation (By similarity).

Phosphorylates MUC1 in breast cancer cells, decreasing the interaction of MUC1 with CTNNB1/beta-catenin (PubMed:9819408).

Is necessary for the establishment of neuronal polarity and axon outgrowth (PubMed:20067585).

Phosphorylates MARK2, leading to inhibit its activity (By similarity).

Phosphorylates SIK1 at 'Thr-182', leading to sustain its activity (PubMed:18348280).

Phosphorylates ZC3HAV1 which enhances its antiviral activity (PubMed:22514281).

Phosphorylates SNAI1, leading to its BTRC-triggered ubiquitination and proteasomal degradation (PubMed:15448698, PubMed:15647282).

Phosphorylates SFPQ at 'Thr-687' upon T-cell activation (PubMed:20932480).

Phosphorylates NR1D1 st 'Ser-55' and 'Ser-59' and stabilizes it by protecting it from proteasomal degradation. Regulates the circadian clock via phosphorylation of the major clock components including ARNTL/BMAL1, CLOCK and PER2 (PubMed:19946213, PubMed:28903391).

Phosphorylates CLOCK AT 'Ser-427' and targets it for proteasomal degradation (PubMed:19946213).

Phosphorylates ARNTL/BMAL1 at 'Ser-17' and 'Ser-21' and primes it for ubiquitination and proteasomal degradation (PubMed:28903391).

Phosphorylates OGT at 'Ser-3' or 'Ser-4' which positively regulates its activity. Phosphorylates MYCN in neuroblastoma cells which may promote its degradation (PubMed:24391509).

Regulates the circadian rhythmicity of hippocampal long-term potentiation and ARNTL/BMLA1 and PER2 expression (By similarity).

Acts as a regulator of autophagy by mediating phosphorylation of KAT5/TIP60 under starvation conditions, leading to activate KAT5/TIP60 acetyltransferase activity and promote acetylation of key autophagy regulators, such as ULK1 and RUBCNL/Pacer (PubMed:30704899).

Negatively regulates extrinsic apoptotic signaling pathway via death domain receptors. Promotes the formation of an anti-apoptotic complex, made of DDX3X, BRIC2 and GSK3B, at death receptors, including TNFRSF10B. The anti-apoptotic function is most effective with weak apoptotic signals and can be overcome by stronger stimulation (PubMed:18846110).

Phosphorylates E2F1, promoting the interaction between E2F1 and USP11, leading to stabilize E2F1 and promote its activity (PubMed:17050006, PubMed:28992046).
Biological Process
Beta-catenin destruction complex disassembly Source: ComplexPortal
Cellular response to amyloid-beta Source: ARUK-UCL
Cellular response to interleukin-3 Source: UniProtKB
Cellular response to retinoic acid Source: ARUK-UCL
Circadian rhythm Source: UniProtKB
Dopamine receptor signaling pathway Source: ParkinsonsUK-UCL
Epithelial to mesenchymal transition Source: UniProtKB
ER overload response Source: MGI
Establishment of cell polarity Source: ARUK-UCL
Excitatory postsynaptic potential Source: ParkinsonsUK-UCL
Extrinsic apoptotic signaling pathway Source: ARUK-UCL
Extrinsic apoptotic signaling pathway in absence of ligand Source: UniProtKB
Glycogen metabolic process Source: BHF-UCL
Hippocampus development Source: BHF-UCL
Insulin receptor signaling pathway Source: GO_Central
Intracellular signal transduction Source: MGI
Maintenance of cell polarity Source: ARUK-UCL
Negative regulation of apoptotic process Source: MGI
Negative regulation of calcineurin-NFAT signaling cascade Source: UniProtKB
Negative regulation of canonical Wnt signaling pathway Source: ARUK-UCL
Negative regulation of canonical Wnt signaling pathway involved in osteoblast differentiation Source: ARUK-UCL
Negative regulation of dopaminergic neuron differentiation Source: ParkinsonsUK-UCL
Negative regulation of extrinsic apoptotic signaling pathway via death domain receptors Source: UniProtKB
Negative regulation of gene expression Source: ARUK-UCL
Negative regulation of glycogen (starch) synthase activity Source: UniProtKB
Negative regulation of glycogen biosynthetic process Source: UniProtKB
Negative regulation of mesenchymal stem cell differentiation Source: ARUK-UCL
Negative regulation of neuron death Source: UniProtKB
Negative regulation of phosphoprotein phosphatase activity Source: ARUK-UCL
Negative regulation of protein acetylation Source: ARUK-UCL
Negative regulation of protein binding Source: BHF-UCL
Negative regulation of protein-containing complex assembly Source: BHF-UCL
Negative regulation of protein localization to nucleus Source: BHF-UCL
Negative regulation of type B pancreatic cell development Source: UniProtKB
Neuron projection development Source: UniProtKB
Neuron projection organization Source: ARUK-UCL
Peptidyl-serine phosphorylation Source: ParkinsonsUK-UCL
Peptidyl-threonine phosphorylation Source: ParkinsonsUK-UCL
Positive regulation of autophagy Source: UniProtKB
Positive regulation of cell differentiation Source: ARUK-UCL
Positive regulation of cell-matrix adhesion Source: BHF-UCL
Positive regulation of cilium assembly Source: UniProtKB
Positive regulation of gene expression Source: ARUK-UCL
Positive regulation of GTPase activity Source: BHF-UCL
Positive regulation of mitochondrial outer membrane permeabilization involved in apoptotic signaling pathway Source: UniProtKB
Positive regulation of mitochondrion organization Source: ParkinsonsUK-UCL
Positive regulation of neuron death Source: ParkinsonsUK-UCL
Positive regulation of proteasomal ubiquitin-dependent protein catabolic process Source: FlyBase
Positive regulation of protein binding Source: UniProtKB
Positive regulation of protein catabolic process Source: BHF-UCL
Positive regulation of protein-containing complex assembly Source: BHF-UCL
Positive regulation of protein export from nucleus Source: MGI
Positive regulation of protein localization to centrosome Source: ARUK-UCL
Positive regulation of protein localization to cilium Source: UniProtKB
Protein autophosphorylation Source: UniProtKB
Protein phosphorylation Source: UniProtKB
Regulation of axon extension Source: ARUK-UCL
Regulation of axonogenesis Source: ARUK-UCL
Regulation of cellular response to heat Source: Reactome
Regulation of circadian rhythm Source: UniProtKB
Regulation of dendrite morphogenesis Source: ARUK-UCL
Regulation of long-term synaptic potentiation Source: UniProtKB
Regulation of microtubule anchoring at centrosome Source: ARUK-UCL
Regulation of microtubule-based process Source: UniProtKB
Regulation of microtubule cytoskeleton organization Source: ARUK-UCL
Regulation of neuron projection development Source: GO_Central
Regulation of protein export from nucleus Source: ComplexPortal
Regulation of synaptic vesicle exocytosis Source: SynGO
Signal transduction Source: GO_Central
Superior temporal gyrus development Source: BHF-UCL
Viral protein processing Source: Reactome
Cellular Location
Cytoplasm; Cell membrane; Nucleus. The phosphorylated form shows localization to cytoplasm and cell membrane (PubMed:20937854). The MEMO1-RHOA-DIAPH1 signaling pathway controls localization of the phosphorylated form to the cell membrane (PubMed:20937854).
PTM
Phosphorylated by AKT1 and ILK1. Upon insulin-mediated signaling, the activated PKB/AKT1 protein kinase phosphorylates and desactivates GSK3B, resulting in the dephosphorylation and activation of GYS1. Activated by phosphorylation at Tyr-216 (PubMed:25169422). Inactivated by phosphorylation at Ser-9 (Probable). Phosphorylated in a circadian manner in the hippocampus (By similarity).
Mono-ADP-ribosylation by PARP10 negatively regulates kinase activity.

Ryu, H. Y., Kim, L. E., Jeong, H., Yeo, B. K., Lee, J. W., Nam, H., ... & Yu, S. W. (2021). GSK3B induces autophagy by phosphorylating ULK1. Experimental & Molecular Medicine, 53(3), 369-383.

Sakellariou, D., Tiberti, M., Kleiber, T. H., Blazquez, L., López, A. R., Abildgaard, M. H., ... & Frankel, L. B. (2021). eIF4A3 regulates the TFEB-mediated transcriptional response via GSK3B to control autophagy. Cell Death & Differentiation, 28(12), 3344-3356.

Kim, J., Shin, J. Y., Choi, Y. H., Lee, S. Y., Jin, M. H., Kim, C. D., ... & Lee, S. (2021). Adenosine and cordycepin accelerate tissue remodeling process through adenosine receptor mediated Wnt/β-catenin pathway stimulation by regulating GSK3b activity. International journal of molecular sciences, 22(11), 5571.

Liu, Z., Li, Y., Li, X., Zhao, J., Wu, S., Wu, H., & Gou, S. (2020). Overexpression of YBX1 promotes pancreatic ductal adenocarcinoma growth via the GSK3B/Cyclin D1/Cyclin E1 pathway. Molecular Therapy-Oncolytics, 17, 21-30.

Lee, H., Shin, W., Kim, K., Lee, S., Lee, E. J., Kim, J., ... & Kim, E. (2019). NGL-3 in the regulation of brain development, Akt/GSK3b signaling, long-term depression, and locomotive and cognitive behaviors. PLoS biology, 17(6), e2005326.

Wu, H., Lu, X. X., Wang, J. R., Yang, T. Y., Li, X. M., He, X. S., ... & Li, J. M. (2019). TRAF6 inhibits colorectal cancer metastasis through regulating selective autophagic CTNNB1/β-catenin degradation and is targeted for GSK3B/GSK3β-mediated phosphorylation and degradation. Autophagy, 15(9), 1506-1522.

Garcia-Lacarte, M., Mansego, M. L., Zulet, M. A., Martinez, J. A., & Milagro, F. I. (2019). miR-1185-1 and miR-548q are biomarkers of response to weight loss and regulate the expression of GSK3B. Cells, 8(12), 1548.

Edderkaoui, M., Chheda, C., Soufi, B., Zayou, F., Hu, R. W., Ramanujan, V. K., ... & Pandol, S. J. (2018). An inhibitor of GSK3B and HDACs kills pancreatic cancer cells and slows pancreatic tumor growth and metastasis in mice. Gastroenterology, 155(6), 1985-1998.

Li, K. L., & Lin, Y. C. (2018). PM2. 5 induced cardiac hypertrophy via CREB/GSK3b/SOS1 pathway and metabolomics alterations. Oncotarget, 9(56), 30748.

Jorge-Torres, O. C., Szczesna, K., Roa, L., Casal, C., Gonzalez-Somermeyer, L., Soler, M., ... & Esteller, M. (2018). Inhibition of Gsk3b reduces Nfkb1 signaling and rescues synaptic activity to improve the Rett syndrome phenotype in Mecp2-knockout mice. Cell Reports, 23(6), 1665-1677.

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For research use only. Not intended for any clinical use.

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