Browse GSK3B

Summary
SymbolGSK3B
Nameglycogen synthase kinase 3 beta
Aliases GSK-3 beta; GSK3beta isoform; serine/threonine-protein kinase GSK3B; Glycogen synthase kinase-3 beta
Chromosomal Location3q13.3
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Basic function annotation.
> Subcellular Location, Domain and Function
> Gene Ontology
> KEGG and Reactome Pathway
> Subcellular Location, Domain and Function
 
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.
Domain PF00069 Protein kinase domain
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 (PubMed:24391509).

> Gene Ontology
 
Biological Process GO:0000271 polysaccharide biosynthetic process
GO:0000320 re-entry into mitotic cell cycle
GO:0000768 syncytium formation by plasma membrane fusion
GO:0001558 regulation of cell growth
GO:0001837 epithelial to mesenchymal transition
GO:0001952 regulation of cell-matrix adhesion
GO:0001954 positive regulation of cell-matrix adhesion
GO:0002064 epithelial cell development
GO:0002065 columnar/cuboidal epithelial cell differentiation
GO:0002066 columnar/cuboidal epithelial cell development
GO:0002067 glandular epithelial cell differentiation
GO:0002068 glandular epithelial cell development
GO:0003012 muscle system process
GO:0003300 cardiac muscle hypertrophy
GO:0003309 type B pancreatic cell differentiation
GO:0003323 type B pancreatic cell development
GO:0005976 polysaccharide metabolic process
GO:0005977 glycogen metabolic process
GO:0005978 glycogen biosynthetic process
GO:0005979 regulation of glycogen biosynthetic process
GO:0005996 monosaccharide metabolic process
GO:0006006 glucose metabolic process
GO:0006073 cellular glucan metabolic process
GO:0006091 generation of precursor metabolites and energy
GO:0006109 regulation of carbohydrate metabolic process
GO:0006112 energy reserve metabolic process
GO:0006304 DNA modification
GO:0006305 DNA alkylation
GO:0006306 DNA methylation
GO:0006349 regulation of gene expression by genetic imprinting
GO:0006606 protein import into nucleus
GO:0006611 protein export from nucleus
GO:0006839 mitochondrial transport
GO:0006913 nucleocytoplasmic transport
GO:0006949 syncytium formation
GO:0006983 ER overload response
GO:0006984 ER-nucleus signaling pathway
GO:0007006 mitochondrial membrane organization
GO:0007160 cell-matrix adhesion
GO:0007212 dopamine receptor signaling pathway
GO:0007409 axonogenesis
GO:0007520 myoblast fusion
GO:0007623 circadian rhythm
GO:0008361 regulation of cell size
GO:0008637 apoptotic mitochondrial changes
GO:0009250 glucan biosynthetic process
GO:0009266 response to temperature stimulus
GO:0009408 response to heat
GO:0009894 regulation of catabolic process
GO:0009896 positive regulation of catabolic process
GO:0010498 proteasomal protein catabolic process
GO:0010611 regulation of cardiac muscle hypertrophy
GO:0010614 negative regulation of cardiac muscle hypertrophy
GO:0010675 regulation of cellular carbohydrate metabolic process
GO:0010677 negative regulation of cellular carbohydrate metabolic process
GO:0010720 positive regulation of cell development
GO:0010721 negative regulation of cell development
GO:0010769 regulation of cell morphogenesis involved in differentiation
GO:0010770 positive regulation of cell morphogenesis involved in differentiation
GO:0010799 regulation of peptidyl-threonine phosphorylation
GO:0010800 positive regulation of peptidyl-threonine phosphorylation
GO:0010810 regulation of cell-substrate adhesion
GO:0010811 positive regulation of cell-substrate adhesion
GO:0010821 regulation of mitochondrion organization
GO:0010822 positive regulation of mitochondrion organization
GO:0010906 regulation of glucose metabolic process
GO:0010962 regulation of glucan biosynthetic process
GO:0010975 regulation of neuron projection development
GO:0010976 positive regulation of neuron projection development
GO:0010977 negative regulation of neuron projection development
GO:0014041 regulation of neuron maturation
GO:0014043 negative regulation of neuron maturation
GO:0014741 negative regulation of muscle hypertrophy
GO:0014743 regulation of muscle hypertrophy
GO:0014896 muscle hypertrophy
GO:0014897 striated muscle hypertrophy
GO:0014902 myotube differentiation
GO:0015980 energy derivation by oxidation of organic compounds
GO:0016049 cell growth
GO:0016051 carbohydrate biosynthetic process
GO:0016055 Wnt signaling pathway
GO:0017038 protein import
GO:0018105 peptidyl-serine phosphorylation
GO:0018107 peptidyl-threonine phosphorylation
GO:0018209 peptidyl-serine modification
GO:0018210 peptidyl-threonine modification
GO:0019318 hexose metabolic process
GO:0021537 telencephalon development
GO:0021543 pallium development
GO:0021700 developmental maturation
GO:0021761 limbic system development
GO:0021766 hippocampus development
GO:0021987 cerebral cortex development
GO:0022604 regulation of cell morphogenesis
GO:0030111 regulation of Wnt signaling pathway
GO:0030178 negative regulation of Wnt signaling pathway
GO:0030307 positive regulation of cell growth
GO:0030516 regulation of axon extension
GO:0030856 regulation of epithelial cell differentiation
GO:0030857 negative regulation of epithelial cell differentiation
GO:0030900 forebrain development
GO:0031016 pancreas development
GO:0031018 endocrine pancreas development
GO:0031329 regulation of cellular catabolic process
GO:0031331 positive regulation of cellular catabolic process
GO:0031333 negative regulation of protein complex assembly
GO:0031334 positive regulation of protein complex assembly
GO:0031345 negative regulation of cell projection organization
GO:0031346 positive regulation of cell projection organization
GO:0031589 cell-substrate adhesion
GO:0032091 negative regulation of protein binding
GO:0032092 positive regulation of protein binding
GO:0032259 methylation
GO:0032386 regulation of intracellular transport
GO:0032387 negative regulation of intracellular transport
GO:0032388 positive regulation of intracellular transport
GO:0032434 regulation of proteasomal ubiquitin-dependent protein catabolic process
GO:0032436 positive regulation of proteasomal ubiquitin-dependent protein catabolic process
GO:0032535 regulation of cellular component size
GO:0032881 regulation of polysaccharide metabolic process
GO:0032885 regulation of polysaccharide biosynthetic process
GO:0032886 regulation of microtubule-based process
GO:0032984 macromolecular complex disassembly
GO:0033135 regulation of peptidyl-serine phosphorylation
GO:0033138 positive regulation of peptidyl-serine phosphorylation
GO:0033157 regulation of intracellular protein transport
GO:0033692 cellular polysaccharide biosynthetic process
GO:0034504 protein localization to nucleus
GO:0034605 cellular response to heat
GO:0034637 cellular carbohydrate biosynthetic process
GO:0034976 response to endoplasmic reticulum stress
GO:0035270 endocrine system development
GO:0035372 protein localization to microtubule
GO:0035728 response to hepatocyte growth factor
GO:0035729 cellular response to hepatocyte growth factor stimulus
GO:0035794 positive regulation of mitochondrial membrane permeability
GO:0035883 enteroendocrine cell differentiation
GO:0036015 response to interleukin-3
GO:0036016 cellular response to interleukin-3
GO:0038034 signal transduction in absence of ligand
GO:0040029 regulation of gene expression, epigenetic
GO:0042176 regulation of protein catabolic process
GO:0042306 regulation of protein import into nucleus
GO:0042308 negative regulation of protein import into nucleus
GO:0042551 neuron maturation
GO:0042692 muscle cell differentiation
GO:0042990 regulation of transcription factor import into nucleus
GO:0042991 transcription factor import into nucleus
GO:0042992 negative regulation of transcription factor import into nucleus
GO:0043161 proteasome-mediated ubiquitin-dependent protein catabolic process
GO:0043241 protein complex disassembly
GO:0043254 regulation of protein complex assembly
GO:0043255 regulation of carbohydrate biosynthetic process
GO:0043393 regulation of protein binding
GO:0043414 macromolecule methylation
GO:0043467 regulation of generation of precursor metabolites and energy
GO:0043500 muscle adaptation
GO:0043502 regulation of muscle adaptation
GO:0044026 DNA hypermethylation
GO:0044027 hypermethylation of CpG island
GO:0044030 regulation of DNA methylation
GO:0044042 glucan metabolic process
GO:0044057 regulation of system process
GO:0044089 positive regulation of cellular component biogenesis
GO:0044262 cellular carbohydrate metabolic process
GO:0044264 cellular polysaccharide metabolic process
GO:0044337 canonical Wnt signaling pathway involved in positive regulation of apoptotic process
GO:0044380 protein localization to cytoskeleton
GO:0044723 single-organism carbohydrate metabolic process
GO:0044728 DNA methylation or demethylation
GO:0044744 protein targeting to nucleus
GO:0045444 fat cell differentiation
GO:0045665 negative regulation of neuron differentiation
GO:0045666 positive regulation of neuron differentiation
GO:0045719 negative regulation of glycogen biosynthetic process
GO:0045732 positive regulation of protein catabolic process
GO:0045773 positive regulation of axon extension
GO:0045785 positive regulation of cell adhesion
GO:0045862 positive regulation of proteolysis
GO:0045912 negative regulation of carbohydrate metabolic process
GO:0045927 positive regulation of growth
GO:0046777 protein autophosphorylation
GO:0046822 regulation of nucleocytoplasmic transport
GO:0046823 negative regulation of nucleocytoplasmic transport
GO:0046824 positive regulation of nucleocytoplasmic transport
GO:0046825 regulation of protein export from nucleus
GO:0046827 positive regulation of protein export from nucleus
GO:0046902 regulation of mitochondrial membrane permeability
GO:0048469 cell maturation
GO:0048511 rhythmic process
GO:0048588 developmental cell growth
GO:0048638 regulation of developmental growth
GO:0048639 positive regulation of developmental growth
GO:0048667 cell morphogenesis involved in neuron differentiation
GO:0048675 axon extension
GO:0048762 mesenchymal cell differentiation
GO:0048863 stem cell differentiation
GO:0050768 negative regulation of neurogenesis
GO:0050769 positive regulation of neurogenesis
GO:0050770 regulation of axonogenesis
GO:0050772 positive regulation of axonogenesis
GO:0051051 negative regulation of transport
GO:0051052 regulation of DNA metabolic process
GO:0051098 regulation of binding
GO:0051099 positive regulation of binding
GO:0051100 negative regulation of binding
GO:0051146 striated muscle cell differentiation
GO:0051168 nuclear export
GO:0051169 nuclear transport
GO:0051170 nuclear import
GO:0051222 positive regulation of protein transport
GO:0051224 negative regulation of protein transport
GO:0051348 negative regulation of transferase activity
GO:0051531 NFAT protein import into nucleus
GO:0051532 regulation of NFAT protein import into nucleus
GO:0051534 negative regulation of NFAT protein import into nucleus
GO:0051961 negative regulation of nervous system development
GO:0051962 positive regulation of nervous system development
GO:0060070 canonical Wnt signaling pathway
GO:0060485 mesenchyme development
GO:0060560 developmental growth involved in morphogenesis
GO:0060828 regulation of canonical Wnt signaling pathway
GO:0061136 regulation of proteasomal protein catabolic process
GO:0061387 regulation of extent of cell growth
GO:0061564 axon development
GO:0070059 intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress
GO:0070873 regulation of glycogen metabolic process
GO:0070874 negative regulation of glycogen metabolic process
GO:0070997 neuron death
GO:0071109 superior temporal gyrus development
GO:0071216 cellular response to biotic stimulus
GO:0071514 genetic imprinting
GO:0071542 dopaminergic neuron differentiation
GO:0072698 protein localization to microtubule cytoskeleton
GO:0090066 regulation of anatomical structure size
GO:0090090 negative regulation of canonical Wnt signaling pathway
GO:0090257 regulation of muscle system process
GO:0090316 positive regulation of intracellular protein transport
GO:0090317 negative regulation of intracellular protein transport
GO:0090559 regulation of membrane permeability
GO:0097191 extrinsic apoptotic signaling pathway
GO:0097192 extrinsic apoptotic signaling pathway in absence of ligand
GO:0097193 intrinsic apoptotic signaling pathway
GO:0097345 mitochondrial outer membrane permeabilization
GO:0099565 chemical synaptic transmission, postsynaptic
GO:0198738 cell-cell signaling by wnt
GO:1900034 regulation of cellular response to heat
GO:1900180 regulation of protein localization to nucleus
GO:1900181 negative regulation of protein localization to nucleus
GO:1901028 regulation of mitochondrial outer membrane permeabilization involved in apoptotic signaling pathway
GO:1901030 positive regulation of mitochondrial outer membrane permeabilization involved in apoptotic signaling pathway
GO:1901214 regulation of neuron death
GO:1901216 positive regulation of neuron death
GO:1901800 positive regulation of proteasomal protein catabolic process
GO:1902108 regulation of mitochondrial membrane permeability involved in apoptotic process
GO:1902110 positive regulation of mitochondrial membrane permeability involved in apoptotic process
GO:1902593 single-organism nuclear import
GO:1902686 mitochondrial outer membrane permeabilization involved in programmed cell death
GO:1903050 regulation of proteolysis involved in cellular protein catabolic process
GO:1903052 positive regulation of proteolysis involved in cellular protein catabolic process
GO:1903362 regulation of cellular protein catabolic process
GO:1903364 positive regulation of cellular protein catabolic process
GO:1903429 regulation of cell maturation
GO:1903430 negative regulation of cell maturation
GO:1903533 regulation of protein targeting
GO:1903828 negative regulation of cellular protein localization
GO:1903829 positive regulation of cellular protein localization
GO:1904338 regulation of dopaminergic neuron differentiation
GO:1904339 negative regulation of dopaminergic neuron differentiation
GO:1904589 regulation of protein import
GO:1904590 negative regulation of protein import
GO:1904885 beta-catenin destruction complex assembly
GO:1904886 beta-catenin destruction complex disassembly
GO:1904950 negative regulation of establishment of protein localization
GO:1904951 positive regulation of establishment of protein localization
GO:1990138 neuron projection extension
GO:2000074 regulation of type B pancreatic cell development
GO:2000077 negative regulation of type B pancreatic cell development
GO:2000465 regulation of glycogen (starch) synthase activity
GO:2000466 negative regulation of glycogen (starch) synthase activity
GO:2000736 regulation of stem cell differentiation
GO:2000738 positive regulation of stem cell differentiation
GO:2001233 regulation of apoptotic signaling pathway
GO:2001235 positive regulation of apoptotic signaling pathway
Molecular Function GO:0001085 RNA polymerase II transcription factor binding
GO:0002039 p53 binding
GO:0004674 protein serine/threonine kinase activity
GO:0008013 beta-catenin binding
GO:0008134 transcription factor binding
GO:0031625 ubiquitin protein ligase binding
GO:0034236 protein kinase A catalytic subunit binding
GO:0044389 ubiquitin-like protein ligase binding
GO:0050321 tau-protein kinase activity
GO:0051018 protein kinase A binding
GO:0051059 NF-kappaB binding
Cellular Component GO:0005813 centrosome
GO:0030425 dendrite
GO:0030426 growth cone
GO:0030427 site of polarized growth
GO:0030877 beta-catenin destruction complex
GO:0043025 neuronal cell body
GO:0043198 dendritic shaft
GO:0044297 cell body
GO:0098794 postsynapse
GO:1990909 Wnt signalosome
> KEGG and Reactome Pathway
 
KEGG hsa04012 ErbB signaling pathway
hsa04062 Chemokine signaling pathway
hsa04110 Cell cycle
hsa04150 mTOR signaling pathway
hsa04151 PI3K-Akt signaling pathway
hsa04310 Wnt signaling pathway
hsa04340 Hedgehog signaling pathway
hsa04360 Axon guidance
hsa04390 Hippo signaling pathway
hsa04510 Focal adhesion
hsa04550 Signaling pathways regulating pluripotency of stem cells
hsa04660 T cell receptor signaling pathway
hsa04662 B cell receptor signaling pathway
hsa04722 Neurotrophin signaling pathway
hsa04728 Dopaminergic synapse
hsa04910 Insulin signaling pathway
hsa04916 Melanogenesis
hsa04917 Prolactin signaling pathway
hsa04919 Thyroid hormone signaling pathway
Reactome R-HSA-198323: AKT phosphorylates targets in the cytosol
R-HSA-4839748: AMER1 mutants destabilize the destruction complex
R-HSA-5467337: APC truncation mutants have impaired AXIN binding
R-HSA-5467340: AXIN missense mutants destabilize the destruction complex
R-HSA-4839735: AXIN mutants destabilize the destruction complex, activating WNT signaling
R-HSA-1280218: Adaptive Immune System
R-HSA-422475: Axon guidance
R-HSA-5250924: B-WICH complex positively regulates rRNA expression
R-HSA-196299: Beta-catenin phosphorylation cascade
R-HSA-399956: CRMPs in Sema3A signaling
R-HSA-3371556: Cellular response to heat stress
R-HSA-2262752: Cellular responses to stress
R-HSA-5674400: Constitutive Signaling by AKT1 E17K in Cancer
R-HSA-2172127: DAP12 interactions
R-HSA-2424491: DAP12 signaling
R-HSA-5610783: Degradation of GLI2 by the proteasome
R-HSA-195253: Degradation of beta-catenin by the destruction complex
R-HSA-1266738: Developmental Biology
R-HSA-4641262: Disassembly of the destruction complex and recruitment of AXIN to the membrane
R-HSA-1643685: Disease
R-HSA-5663202: Diseases of signal transduction
R-HSA-186763: Downstream signal transduction
R-HSA-1168372: Downstream signaling events of B Cell Receptor (BCR)
R-HSA-212165: Epigenetic regulation of gene expression
R-HSA-2454202: Fc epsilon receptor (FCERI) signaling
R-HSA-180292: GAB1 signalosome
R-HSA-5610785: GLI3 is processed to GLI3R by the proteasome
R-HSA-74160: Gene Expression
R-HSA-5610787: Hedgehog 'off' state
R-HSA-168256: Immune System
R-HSA-168249: Innate Immune System
R-HSA-5339716: Misspliced GSK3beta mutants stabilize beta-catenin
R-HSA-187037: NGF signalling via TRKA from the plasma membrane
R-HSA-2219528: PI3K/AKT Signaling in Cancer
R-HSA-198203: PI3K/AKT activation
R-HSA-1257604: PIP3 activates AKT signaling
R-HSA-5250913: Positive epigenetic regulation of rRNA expression
R-HSA-3371453: Regulation of HSF1-mediated heat shock response
R-HSA-2730905: Role of LAT2/NTAL/LAB on calcium mobilization
R-HSA-5358747: S33 mutants of beta-catenin aren't phosphorylated
R-HSA-5358749: S37 mutants of beta-catenin aren't phosphorylated
R-HSA-5358751: S45 mutants of beta-catenin aren't phosphorylated
R-HSA-373755: Semaphorin interactions
R-HSA-162582: Signal Transduction
R-HSA-177929: Signaling by EGFR
R-HSA-5358351: Signaling by Hedgehog
R-HSA-186797: Signaling by PDGF
R-HSA-1433557: Signaling by SCF-KIT
R-HSA-4791275: Signaling by WNT in cancer
R-HSA-195721: Signaling by Wnt
R-HSA-983705: Signaling by the B Cell Receptor (BCR)
R-HSA-166520: Signalling by NGF
R-HSA-5358752: T41 mutants of beta-catenin aren't phosphorylated
R-HSA-201681: TCF dependent signaling in response to WNT
R-HSA-5467348: Truncations of AMER1 destabilize the destruction complex
R-HSA-4839743: phosphorylation site mutants of CTNNB1 are not targeted to the proteasome by the destruction complex
R-HSA-4839744: truncated APC mutants destabilize the destruction complex
Summary
SymbolGSK3B
Nameglycogen synthase kinase 3 beta
Aliases GSK-3 beta; GSK3beta isoform; serine/threonine-protein kinase GSK3B; Glycogen synthase kinase-3 beta
Chromosomal Location3q13.3
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Literatures that report relations between GSK3B and anti-tumor immunity. The specific mechanism were also collected if the literature reports that a gene specifically promotes or inhibits the infiltration or function of T/NK cells.
> Text Mining
 
  Literatures describing the relation between GSK3B and anti-tumor immunity in human cancer.
PMID Cancer type Relation to immunity Evidence sentences
25814664ThymomaPromote immunity (T cell function)Taken together, DC-based immune response mediated by interferon-γ-induced IDO expression via GSK-3β activity not only regulates CD8(+) T-cell proliferation and cytotoxic T lymphocyte activity but also modulates OVA-pulsed DC vaccination against EG7 thymoma.
23509364Breast Carcinoma; Hepatocellular CarcinomaInhibit immunityNK group 2, member D (NKG2D) is an NK cell-activating receptor crucially involved in cancer immunosurveillance. In this study, we show that induction of EMT by TGF-β stimulation of human keratinocytes, by glycogen synthase kinase-3β inhibition in several epithelial tumor cell lines, and by Snail1 overexpression in colorectal cancer cells strongly upregulated the expression of NKG2D ligands (NKG2DLs), MHC class I chain-related molecules A and B (MICA/B) and ULBP1-3.
27572267Basal-Like Breast CarcinomaPromote immunity (T cell function)We also demonstrate that epidermal growth factor (EGF) stabilizes PD-L1 via GSK3β inactivation in basal-like breast cancer. Inhibition of EGF signalling by gefitinib destabilizes PD-L1, enhances antitumour T-cell immunity and therapeutic efficacy of PD-1 blockade in syngeneic mouse models.
29104081Colon CacinomaInhibit immunity (T cell function)In this study, we sought to evaluate whether the activation of the wnt/β-catenin pathway through inhibition of glycogen synthase kinase-3β (GSK-3β) using 4,6-disubstituted pyrrolopyrimidine (TWS119) could be an efficient strategy to improve the proliferation, differentiation and cytolytic activity of γδT cells against colon cancer cells. Remarkably, we found that TWS119 significantly enhanced the proliferation and survival of γδT cells via activation of the mammalian target of rapamycin (mTOR) pathway, upregulation of the expression of the anti-apoptotic protein Bcl-2 and inhibition of cleaved caspase-3 in addition to the Wnt pathway.
Summary
SymbolGSK3B
Nameglycogen synthase kinase 3 beta
Aliases GSK-3 beta; GSK3beta isoform; serine/threonine-protein kinase GSK3B; Glycogen synthase kinase-3 beta
Chromosomal Location3q13.3
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content High-throughput screening data (e.g. CRISPR-Cas9, shRNA and RNAi) for T cell-mediated killing. Genetic screen techniques can identify mechanisms of tumor cell resistance (e.g., PTPN2) and sensitivity (e.g., APLNR) to killing by cytotoxic T cells, the central effectors of anti-tumor immunity. After comprehensively searching, eight groups of screening data sets were collected in the current database. In this tab, users can check whether their selected genes cause resistance or increase sensitivity to T cell-mediated killing in various data sets.
> High-throughput Screening
  Statistical results of GSK3B in screening data sets for detecting immune reponses.
PMID Screening System Cancer Type Cell Line Data Set Statistical Results Relation to immunity
29301958CRISPR-Cas9 melanomaB16F10Pmel-1 T cell NA/NS NA/NS
29301958CRISPR-Cas9 melanomaB16F10OT-1 T cell NA/NS NA/NS
28783722CRISPR-Cas9 melanomaMel6242CT-CRISPR NA/NS NA/NS
28723893CRISPR-Cas9 melanomaB16GVAX+Anti-PD1 NA/NS NA/NS
28723893CRISPR-Cas9 melanomaB16GVAX NA/NS NA/NS
25691366RNAiBreast cancerMCF7Luc-CTL assay NA/NS NA/NS
24476824shRNAmelanomaB16Primary screen NA/NS NA/NS
24476824shRNAmelanomaB16Secondary screen Total # shRNA with >= 4-fold: 3 Resistant to T-cell proliferation
Summary
SymbolGSK3B
Nameglycogen synthase kinase 3 beta
Aliases GSK-3 beta; GSK3beta isoform; serine/threonine-protein kinase GSK3B; Glycogen synthase kinase-3 beta
Chromosomal Location3q13.3
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Transcriptomic and genomic profiling of pre-treated tumor biopsies from responders and non-responders to immunotherapy. These data were used to identify signatures and mechanisms of response to checkpoint blockade (e.g., anti-PDL1 and anti-PD1). One example is that mutations in the gene PBRM1 benefit clinical survival of patients with clear cell renal cell carcinoma. After comprehensively searching, we collected 5 and 6 of transcriptomic and genomic data sets, respectively. In this tab, users can check whether their selected genes have significant difference of expression or mutation between responders and non-responders in various data sets.
> Expression difference between responders and non-responders
> Mutation difference between responders and non-responders
> Expression difference between responders and non-responders
 
Points in the above scatter plot represent the expression difference of GSK3B in various data sets.
No PMID Cancer type Group Drug # Res # NRes Log2 (Fold Change) P value Anno
126997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)14120.2190.411
226997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)650.7150.676
326997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)87-0.1410.909
428552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 9160.2850.313
528552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 590.0750.969
628552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 470.5490.825
729033130MelanomaallAnti-PD-1 (nivolumab) 2623-0.170.687
829033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 1511-0.1480.937
929033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 1112-0.1590.937
1029301960Clear cell renal cell carcinoma (ccRCC)allAnti-PD-1 (nivolumab) 480.6080.626
1129301960Clear cell renal cell carcinoma (ccRCC)VEGFRiAnti-PD-1 (nivolumab) 2001
1229301960Clear cell renal cell carcinoma (ccRCC)non-VEGFRiAnti-PD-1 (nivolumab) 281.1520.533
1329443960Urothelial cancerallAnti-PD-L1 (atezolizumab) 682300.0740.149
> Mutation difference between responders and non-responders
 
Points in the above scatter plot represent the mutation difference of GSK3B in various data sets.
No PMID Cancer type Group Drug # Res # NRes % Mut/Res % Mut/NRes % Diff (R vs NR) Pval Anno
125765070Non-small cell lung cancer (NSCLC)allAnti-PD-1 (pembrolizumab) 14170001
225765070Non-small cell lung cancer (NSCLC)smokingAnti-PD-1 (pembrolizumab) 1030001
325765070Non-small cell lung cancer (NSCLC)non-smokingAnti-PD-1 (pembrolizumab) 4140001
426359337MelanomaallAnti-CTLA-4 (ipilimumab) 27733.703.70.27
526359337MelanomaBRAFiAnti-CTLA-4 (ipilimumab) 0140001
626359337Melanomanon-BRAFiAnti-CTLA-4 (ipilimumab) 27593.703.70.314
726997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)21170001
826997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)860001
926997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)13110001
1028552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 9160001
1128552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 590001
1228552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 470001
1329033130MelanomaallAnti-PD-1 (nivolumab) 38270001
1429033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 22130001
1529033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 16140001
1629301960Clear cell renal cell carcinoma (ccRCC)allAnti-PD-1 (nivolumab) 11130001
1729301960Clear cell renal cell carcinoma (ccRCC)VEGFRiAnti-PD-1 (nivolumab) 610001
1829301960Clear cell renal cell carcinoma (ccRCC)non-VEGFRiAnti-PD-1 (nivolumab) 5120001
Summary
SymbolGSK3B
Nameglycogen synthase kinase 3 beta
Aliases GSK-3 beta; GSK3beta isoform; serine/threonine-protein kinase GSK3B; Glycogen synthase kinase-3 beta
Chromosomal Location3q13.3
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of GSK3B. The immune-related signatures of 28 TIL types from Charoentong's study, which can be viewed in the download page. For each cancer type, the relative abundance of TILs were inferred by using gene set variation analysis (GSVA) based on gene expression profile. In this tab, users can examine which kinds of TILs might be regulated by the current gene.
> Lymphocyte
 
Summary
SymbolGSK3B
Nameglycogen synthase kinase 3 beta
Aliases GSK-3 beta; GSK3beta isoform; serine/threonine-protein kinase GSK3B; Glycogen synthase kinase-3 beta
Chromosomal Location3q13.3
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of GSK3B. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by GSK3B.
> Immunoinhibitor
> Immunostimulator
> MHC molecule
> Immunoinhibitor
 
> Immunostimulator
 
> MHC molecule
 
Summary
SymbolGSK3B
Nameglycogen synthase kinase 3 beta
Aliases GSK-3 beta; GSK3beta isoform; serine/threonine-protein kinase GSK3B; Glycogen synthase kinase-3 beta
Chromosomal Location3q13.3
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of GSK3B. In this tab, users can examine which chemokines (or receptors) might be regulated by the current gene.
> Chemokine
> Receptor
> Chemokine
 
> Receptor
 
Summary
SymbolGSK3B
Nameglycogen synthase kinase 3 beta
Aliases GSK-3 beta; GSK3beta isoform; serine/threonine-protein kinase GSK3B; Glycogen synthase kinase-3 beta
Chromosomal Location3q13.3
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Distribution of GSK3B expression across immune and molecular subtypes.
> Immune subtype
> Molecular subtype
> Immune subtype
 
> Molecular subtype
 
Summary
SymbolGSK3B
Nameglycogen synthase kinase 3 beta
Aliases GSK-3 beta; GSK3beta isoform; serine/threonine-protein kinase GSK3B; Glycogen synthase kinase-3 beta
Chromosomal Location3q13.3
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Associations between GSK3B and clinical features.
> Overall survival analysis
> Cancer stage
> Tumor grade
> Overall survival
 
> Stage
 
> Grade
 
Summary
SymbolGSK3B
Nameglycogen synthase kinase 3 beta
Aliases GSK-3 beta; GSK3beta isoform; serine/threonine-protein kinase GSK3B; Glycogen synthase kinase-3 beta
Chromosomal Location3q13.3
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Drugs targeting GSK3B collected from DrugBank database.
> Drugs from DrugBank database
 

  Details on drugs targeting GSK3B.
ID Name Drug Type Targets #Targets
DB01356LithiumSmall MoleculeGRIA3, GSK3B, IMPA1, IMPA24
DB017723-[3-(2,3-Dihydroxy-Propylamino)-Phenyl]-4-(5-Fluoro-1-Methyl-1h-Indol-3-Yl)-Pyrrole-2,5-DioneSmall MoleculeGSK3B1
DB01793SB-409513Small MoleculeGSK3B1
DB01950N-(4-Methoxybenzyl)-N'-(5-Nitro-1,3-Thiazol-2-Yl)UreaSmall MoleculeGSK3B1
DB02010StaurosporineSmall MoleculeCDK2, CHRM1, CSK, GSK3B, ITK, LCK, MAPKAPK2, PDPK1, PIK3CG, PIM1, ......13
DB02052Indirubin-3'-MonoximeSmall MoleculeAHR, CDK1, CDK2, CDK5, CDK5R1, GSK3B6
DB03444(3e)-6'-Bromo-2,3'-Biindole-2',3(1h,1'h)-Dione 3-OximeSmall MoleculeGSK3B1
DB04014AlsterpaulloneSmall MoleculeCDK1, CDK5, GSK3B3
DB04395Phosphoaminophosphonic Acid-Adenylate EsterSmall MoleculeACTA1, CCT3, CFTR, CSNK2A1, DAPK1, DTYMK, EPHA2, EPHB2, GALK1, GSK ......26
DB070142-(1,3-benzodioxol-5-yl)-5-[(3-fluoro-4-methoxybenzyl)sulfanyl]-1,3,4-oxadiazoleSmall MoleculeGSK3B1
DB070585-[1-(4-methoxyphenyl)-1H-benzimidazol-6-yl]-1,3,4-oxadiazole-2(3H)-thioneSmall MoleculeGSK3B1
DB07149(7S)-2-(2-aminopyrimidin-4-yl)-7-(2-fluoroethyl)-1,5,6,7-tetrahydro-4H-pyrrolo[3,2-c]pyridin-4-oneSmall MoleculeGSK3B1
DB07584N-[2-(5-methyl-4H-1,2,4-triazol-3-yl)phenyl]-7H-pyrrolo[2,3-d]pyrimidin-4-amineSmall MoleculeAKT1, GSK3B2
DB075855-(5-chloro-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridineSmall MoleculeAKT1, GSK3B2
DB076763-({[(3S)-3,4-dihydroxybutyl]oxy}amino)-1H,2'H-2,3'-biindol-2'-oneSmall MoleculeCAMK4, GSK3B2
DB07812N-[(1S)-2-amino-1-phenylethyl]-5-(1H-pyrrolo[2,3-b]pyridin-4-yl)thiophene-2-carboxamideSmall MoleculeAKT2, GSK3B2
DB078594-(4-CHLOROPHENYL)-4-[4-(1H-PYRAZOL-4-YL)PHENYL]PIPERIDINESmall MoleculeAKT2, GSK3B, PKIA, PRKACA4
DB07947ISOQUINOLINE-5-SULFONIC ACID (2-(2-(4-CHLOROBENZYLOXY)ETHYLAMINO)ETHYL)AMIDESmall MoleculeAKT2, GSK3B, PKIA, PRKACA4
DB08073(2S)-1-(1H-INDOL-3-YL)-3-{[5-(3-METHYL-1H-INDAZOL-5-YL)PYRIDIN-3-YL]OXY}PROPAN-2-AMINESmall MoleculeAKT2, GSK3B, PKIA, PRKACA4
DB12129TideglusibSmall MoleculeGSK3B1