Product Details

Purity

Greater than 90% as determined by SDS-PAGE.

Target Names

GSK3B

Uniprot No.

P49841

Research Area

Signal Transduction

Alternative Names

Glycogen Synthase Kinase 3 Beta; Glycogen synthase kinase-3 beta; GSK 3 beta; GSK-3 beta; GSK3B; GSK3B_HUMAN; GSK3beta isoform; Serine/threonine-protein kinase GSK3B

Species

Homo sapiens (Human)

Source

E.coli

Expression Region

1-420aa

Target Protein Sequence

MSGRPRTTSFAESCKPVQQPSAFGSMKVSRDKDGSKVTTVVATPGQGPDRPQEVSYTDTKVIGNGSFGVVYQAKLCDSGELVAIKKVLQDKRFKNRELQIMRKLDHCNIVRLRYFFYSSGEKKDEVYLNLVLDYVPETVYRVARHYSRAKQTLPVIYVKLYMYQLFRSLAYIHSFGICHRDIKPQNLLLDPDTAVLKLCDFGSAKQLVRGEPNVSYICSRYYRAPELIFGATDYTSSIDVWSAGCVLAELLLGQPIFPGDSGVDQLVEIIKVLGTPTREQIREMNPNYTEFKFPQIKAHPWTKVFRPRTPPEAIALCSRLLEYTPTARLTPLEACAHSFFDELRDPNVKLPNGRDTPALFNFTTQELSSNPPLATILIPPHARIQAAASTPTNATAASDANTGDRGQTNNAASASASNST
Note: The complete sequence may include tag sequence, target protein sequence, linker sequence and extra sequence that is translated with the protein sequence for the purpose(s) of secretion, stability, solubility, etc.
If the exact amino acid sequence of this recombinant protein is critical to your application, please explicitly request the full and complete sequence of this protein before ordering.

Mol. Weight

50.7kDa

Protein Length

Full Length

Tag Info

N-terminal 6xHis-tagged

Form

Liquid or Lyophilized powder
Note: We will preferentially ship the format that we have in stock, however, if you have any special requirement for the format, please remark your requirement when placing the order, we will prepare according to your demand.

Buffer

If the delivery form is liquid, the default storage buffer is Tris/PBS-based buffer, 5%-50% glycerol.
Note: If you have any special requirement for the glycerol content, please remark when you place the order.
If the delivery form is lyophilized powder, the buffer before lyophilization is Tris/PBS-based buffer, 6% Trehalose.

Reconstitution

We recommend that this vial be briefly centrifuged prior to opening to bring the contents to the bottom. Please reconstitute protein in deionized sterile water to a concentration of 0.1-1.0 mg/mL.We recommend to add 5-50% of glycerol (final concentration) and aliquot for long-term storage at -20°C/-80°C. Our default final concentration of glycerol is 50%. Customers could use it as reference.

Troubleshooting and FAQs

Protein FAQs

Storage Condition

Store at -20°C/-80°C upon receipt, aliquoting is necessary for mutiple use. Avoid repeated freeze-thaw cycles.

Shelf Life

The shelf life is related to many factors, storage state, buffer ingredients, storage temperature and the stability of the protein itself.
Generally, the shelf life of liquid form is 6 months at -20°C/-80°C. The shelf life of lyophilized form is 12 months at -20°C/-80°C.

Lead Time

3-7 business days

Notes

Repeated freezing and thawing is not recommended. Store working aliquots at 4°C for up to one week.

Datasheet & COA

Please contact us to get it.

Description

The production of this Recombinant Human GSK3B protein started with the GSK3B gene synthesis. And then using recombinant DNA technology, the GSK3B gene was inserted into an expression vector so that we could get the recombinant express plasmid of GSK3B. Transform the plasmid into the cells of E.coli, culture the cells and we could get the desired Recombinant Human GSK3B protein. But the work was not completed, protein purification and a strict QC system were performed in the last step. The purity is 90%+ determined by SDS-PAGE.

GSK3B is a gene providing an instruction of making a protein named glycogen synthase kinase-3 beta (GSK-3 beta) in human. The protein encoded by this gene is also known as serine/threonine-protein kinase GSK3B (GSK3B) and belongs to protein kinase superfamily. GSK3B protein is a kinase that plays a pivotal role in numerous cellular functions from modulation of microtubule dynamics and cell death. Increasing evidence has implied that deregulation of GSK3beta activity in the adult brain is involved in several CNS disorders, such as affective disorders, schizophrenia and neurodegenerative diseases.

Target Background

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. Requires primed phosphorylation of the majority of its substrates. In skeletal muscle, contributes to insulin regulation of glycogen synthesis by phosphorylating and inhibiting GYS1 activity and hence glycogen synthesis. May also mediate the development of insulin resistance by regulating activation of transcription factors. Regulates protein synthesis by controlling the activity of initiation factor 2B (EIF2BE/EIF2B5) in the same manner as glycogen synthase. 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. Phosphorylates JUN at sites proximal to its DNA-binding domain, thereby reducing its affinity for DNA. 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. Phosphorylates MAPT/TAU on 'Thr-548', decreasing significantly MAPT/TAU ability to bind and stabilize microtubules. MAPT/TAU is the principal component of neurofibrillary tangles in Alzheimer disease. Plays an important role in ERBB2-dependent stabilization of microtubules at the cell cortex. Phosphorylates MACF1, inhibiting its binding to microtubules which is critical for its role in bulge stem cell migration and skin wound repair. 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). Negatively regulates replication in pancreatic beta-cells, resulting in apoptosis, loss of beta-cells and diabetes. Through phosphorylation of the anti-apoptotic protein MCL1, may control cell apoptosis in response to growth factors deprivation. Phosphorylates MUC1 in breast cancer cells, decreasing the interaction of MUC1 with CTNNB1/beta-catenin. Is necessary for the establishment of neuronal polarity and axon outgrowth. Phosphorylates MARK2, leading to inhibit its activity. Phosphorylates SIK1 at 'Thr-182', leading to sustain its activity. Phosphorylates ZC3HAV1 which enhances its antiviral activity. Phosphorylates SNAI1, leading to its BTRC-triggered ubiquitination and proteasomal degradation. Phosphorylates SFPQ at 'Thr-687' upon T-cell activation. 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. Phosphorylates CLOCK AT 'Ser-427' and targets it for proteasomal degradation. Phosphorylates ARNTL/BMAL1 at 'Ser-17' and 'Ser-21' and primes it for ubiquitination and proteasomal degradation. Phosphorylates OGT at 'Ser-3' or 'Ser-4' which positively regulates its activity. Phosphorylates MYCN in neuroblastoma cells which may promote its degradation. Regulates the circadian rhythmicity of hippocampal long-term potentiation and ARNTL/BMLA1 and PER2 expression. 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. 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.

Gene References into Functions

our study suggests that GSK3B plays a pivotal role in HCV virion assembly and release mediated in part through inhibition of apolipoprotein synthesis PMID: 28566716
The results demonstrated that 2HF could inhibit EMT, and cell migration and invasion through the Wnt/bcatenin signaling pathway by suppressing GSK3b phosphorylation, betacatenin expression and transactivation. PMID: 30226607
Results show that SK3beta modulates NF-kappaB activation and RelB degradation through phosphorylation of BCL10 providing evidence for a novel regulatory mechanism by which GSK3beta affects NF-kappaB signaling in activated T cells. PMID: 29358699
LINC00222 acts as a tumor suppressor in lung adenocarcinoma, regulating GSK3beta activity to promote tumor cell apoptosis. PMID: 29990868
miR-199b attenuated the inflammatory response at least partly through the GSK3beta/NF-kappaB signaling pathways in monocytes PMID: 29779167
The luciferase reporter system studies affirmed the direct regulation of miR-452 on the 3'-UTR of the GSK3b, which activate the Wnt/b-catenin signaling. The ectopic upregulation of miR-452 significantly inhibited the expression of GSK3b and enhanced colorectal cancer (CRC) proliferation and invasion in vitro and in vivo. PMID: 30253791
Results show GSK-3beta as a direct target of miR-377-3p and its expression is inversely correlated with that of miR-377 in colorectal cancer cells. PMID: 28857252
Data show that glycogen synthase kinase 3 (GSK3) and proto-oncogene proteins B-raf (BRAF)/MAPK signaling converges to control microphthalmia-associated transcription factor MITF (MITF) nuclear export. PMID: 30150413
GSK-3beta expression is associated with non-small cell lung cancer differentiation and GSK-3beta inhibits autophagy and enhances the radiosensitivity of non-small cell lung cancer cells PMID: 29793508
Its signaling pathway regulates phosphorylated tau accumulation in brain of stressed condition. PMID: 29656013
these results indicate that miR124 transection inhibits the growth and aggressive of osteosarcoma, potentially via suppression of TGFbetamediated AKT/GSK3beta/snail family transcriptional repressor 1 (SNAIL1) signaling, suggesting miR124 may be a potential anticancer agent/target for osteosarcoma therapy. PMID: 29488603
miR-150 was upregulated in CNE-2R cells and played roles in radioresistance in CNE-2 cells. Meanwhile, we found that miR-150 directly targeted GSK3beta gene, and radioresistance in CNE-2R cells could be significantly reversed with ectopic GSK3beta expression. PMID: 29516971
As shown in xenograft model of glioblastoma phosphorylation of 53BP1 by GSK3beta was indispensable for DNA double-strand break repair. PMID: 29328365
miR-1301-3p promoted the expansion of prostate cancer stem cells by inhibiting GSK3beta and SFRP1, and activating the Wnt pathway. PMID: 29358129
MMP-9 overexpression and activation are important events occurring during oral squamous cell carcinoma progression/invasion and that this overexpression/activation is regulated by c-Myc, active MMP-2 and inactive GSK3beta mediated pathways. PMID: 29134466
High GSK3B expression is associated with cervical cancer tumorigenesis and metastasis. PMID: 28627610
GSK-3beta activation index is a potential indicator for recurrent inflammation of chronic rhinosinusitis without nasal polyps. PMID: 28714566
our results revealed that Livin induced EMT through the activation of the p38/GSK3beta pathway, which in turn promoted the progression and metastasis of breast cancer, especially for triple-negative breast cancer (TNBC) PMID: 29039608
Findings showed that NOS1AP (rs348624, rs12742393 and rs1415263), DISC1 (rs821633 and rs1000731), DAOA (rs2391191) and GSK3B (rs6438552) SNPs had no association with development of early-onset schizophrenia; however, our finding suggested statistically significant role of the interaction of NOS1AP, DISC1, DAOA and GSK3B polymorphisms in schizophrenia susceptibility. PMID: 29100974
GSK3beta-SKAP-Kif2b signaling axis constitutes a dynamic link between spindle microtubule plus-ends and mitotic chromosomes to achieve faithful cell division. PMID: 27982129
Casein kinase II, glycogen synthase kinase-3, and Ikaros mediated regulation of leukemia has been summarized. (Review) PMID: 28623166
GSK-3 signaling in health and disease has been discussed. (Review) PMID: 28705437
GSK3 interacts with the PI3K/AKT/mTOR signaling network via phosphorylation. (Review) PMID: 28712664
The data suggested that mediators of the Wnt signalling pathway, such as GSK3beta could be important therapeutic targets for early-stage Osteonecrosis of the femoral head. PMID: 29136173
GSK-3beta is critically important for ordered NF-kappaB signalling through modulation of NEMO phosphorylation. PMID: 27929056
GSK-3 is a novel prognostic indicator in leukemia. (Review) PMID: 28499784
GSK3beta may inhibit VRK2 catalytic activity by disrupting its flexibility. The inhibition of VRK2 catalytic activity by GSK3beta may also inhibit VRK2-induced degradation of TRiC, which could suppress polyQ-expanded Htt aggregation. PMID: 27377031
Mast cells deplete stemness features of glioma cells and induce differentiation. Mast cells exert their effect via inactivation of STAT3 through GSK3 beta downregulation. PMID: 28600192
In conclusion, the authors demonstrated that AKT activation prevents apoptosis, partly through inhibition of GSK3beta, resulting in pluripotent stem cells survival. PMID: 27762303
Downregulation of miR-125b regulates apoptosis in human NSCLC through the suppression of the PI3K/Akt/GSK3beta and Wnt/beta-catenin signaling pathways. PMID: 28713974
This study found that GSK3beta mRNA was overexpressed only in patients with initial Alzheimer's Disease, with no effect on the levels of the protein. PMID: 28176663
We demonstrated the activation of GSK-3beta in classical Hodgkin lymphomas resulting in inhibition of the Wnt/beta-catenin signal cascade and the aberrant accumulation of its activated form in nuclei of Hodgkin Reed-Sternberg and Hodgkin cells PMID: 28208230
CB2 activation with sub-micromolar doses of agonists, which could be more similar to endogenous levels of cannabinoids, promote colon cancer progression in a process that involves AKT and GSK3beta. PMID: 27634891
An imbalanced regulation in protein kinases and protein phosphatases is the direct cause of tau hyperphosphorylation in Alzheimer's disease; GSK-3beta and PP2A are the most implicated. (Review) PMID: 28585125
In this review, we have opted to focus on GSK3beta interactions with mitochondria in ischemic heart disease and expand on the therapeutic interventions. PMID: 28421373
axonal impairment in temporal lobe epilepsy may be mediated by NMDAR via GSK-3beta and Cdk5. In addition, inhibiting either NMDARs or GSK-3beta lowered the relative tau phosphorylation level by reversing the decrease of total tau without affecting phosphorylated tau S396 and T231. PMID: 28595035
GSK-3beta was overexpressed in endometrial cancer tissues, and was positively correlated with International Federation of Gynecology and Obstetrics (FIGO) staging, dedifferentiation, and myometrial infiltration depth; GSK-3beta overexpression predicted lower cumulative and relapse-free survival rate PMID: 27050373
WM130 preferentially inhibits hepatic cancer stem-like cells by suppressing AKT/GSK3beta/beta-catenin signaling pathway. PMID: 27783993
MicroRNA-101 reverses temozolomide resistance by inhibition of GSK3beta expression in glioblastoma cells. PMID: 27792996
Gankyrin sustains PI3K/GSK-3beta/beta-catenin signal activation and promotes an aggressive colorectal cancer phenotype and disease progression. PMID: 27835604
Study sows that expression of the active form of GSK- 3beta (tyrosine 216-phosphorylated) was higher in osteosarcoma than osteoblast cells, and demonstrated a critical role for GSK-3beta in sustaining survival and proliferation of osteosarcoma cells. PMID: 27780915
14-3-3zeta and aPKC-iota synergistically facilitate EMT of cholangiocarcinoma via GSK-3beta/Snail signalling pathway. PMID: 27409422
Results indicate that hypoxia increases IL-11 secretion in anaplastic thyroid carcinoma (ATC) cells via HIF-1alpha induction and that IL-11 then induces epithelial-mesenchymal transition (EMT) in these cells via the PI3K/Akt/GSK3beta pathway. PMID: 27487122
High GSK3B expression is associated with drug resistance in breast cancer. PMID: 26895471
Oncogenic miR-19a and miR-19b were up-regulated in lung cancer stem cells which modulated cancer cells activity. miR-19 activated Wnt/beta-catenin pathway via directly targeting Glycogen Synthase Kinase 3 beta. Sulforaphane suppressed lung cancer stem cells through down-regulating miR-19 and inhibiting Wnt/beta-catenin pathway activation. PMID: 28431267
ZIP9 expression affects phosphorylation states of GSK-3beta. PMID: 27654922
High GSK3 expression is associated with prostate cancer. PMID: 26871944
Cytoplasmic aryl hydrocarbon receptor regulates glycogen synthase kinase 3 beta in non-small cell lung cancer cells. PMID: 27752740
ablation of Glut1 attenuated apoptosis and increased drug resistance via upregulation of p-Akt/p-GSK-3beta (Ser9)/beta-catenin/survivin. PMID: 28803837
frequent upregulation of MIF is implicated in the development and progression of esophageal squamous cell carcinoma (ESCC). PMID: 29079416

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Subcellular Location

Cytoplasm. Nucleus. Cell membrane. Note=The phosphorylated form shows localization to cytoplasm and cell membrane. The MEMO1-RHOA-DIAPH1 signaling pathway controls localization of the phosphorylated form to the cell membrane.

Protein Families

Protein kinase superfamily, CMGC Ser/Thr protein kinase family, GSK-3 subfamily

Tissue Specificity

Expressed in testis, thymus, prostate and ovary and weakly expressed in lung, brain and kidney. Colocalizes with EIF2AK2/PKR and TAU in the Alzheimer disease (AD) brain.

Database Links

HGNC: 4617

OMIM: 605004

KEGG: hsa:2932

STRING: 9606.ENSP00000324806

UniGene: Hs.445733

Code	CSB-EP009963HU
Abbreviation	Recombinant Human GSK3B protein
MSDS	MSDS Datasheet
Size	US$306
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Image	(Tris-Glycine gel) Discontinuous SDS-PAGE (reduced) with 5% enrichment gel and 15% separation gel.
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Recombinant Human Glycogen synthase kinase-3 beta (GSK3B)

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