Product: GSK3A/B Mouse monoclonal Antibody
Catalog: BF8003
Description: Mouse monoclonal antibody to GSK3A/B
Application: WB IHC IF/ICC
Reactivity: Human, Mouse, Rat
Mol.Wt.: 46kDa; 47kD(Calculated).
Uniprot: P49841
RRID: AB_2846227

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Product Info

WB 1:500-1:3000, IHC 1:50-1:200, IF/ICC 1:100-1:500
*The optimal dilutions should be determined by the end user.

WB: For western blot detection of denatured protein samples. IHC: For immunohistochemical detection of paraffin sections (IHC-p) or frozen sections (IHC-f) of tissue samples. IF/ICC: For immunofluorescence detection of cell samples. ELISA(peptide): For ELISA detection of antigenic peptide.

Monoclonal [AFfirm036]
GSK3B antibody detects endogenous levels of total GSK3B.
Cite Format: Affinity Biosciences Cat# BF8003, RRID:AB_2846227.
Mouse IgG1 in phosphate buffered saline (without Mg2+ and Ca2+), pH 7.4, 150mM NaCl, 0.02% sodium azide and 50% glycerol. Store at -20 °C. Stable for 12 months from date of receipt.


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;



A synthesized peptide derived from human GSK3 beta.


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.

Glycogen synthase kinase 3 (GSK-3), a serine-threonine kinase with two isoforms (alpha and beta), was originally discovered as a key enzyme in glycogen metabolism. GSK-3 was subsequently shown to function in cell division, proliferation, motility and survival. GSK-3 plays a role in a number of pathological conditions including cancer and diabetes and is increasingly seen as an important component of 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-3beta 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: Akt-mediated phosphorylation at Ser21 of GSK-3α and Ser9 of GSK-3beta, S6K, RSK, PKA and PKC), dephosphorylation (PP1 and PP2A), and by binding to protein complexes (with beta-catenin, axin, CK1 and the APC complex).

PTMs - P49841 As Substrate

Site PTM Type Enzyme
T7 Phosphorylation
T8 Phosphorylation
S9 Phosphorylation P05129 (PRKCG) , Q05513 (PRKCZ) , P31751 (AKT2) , Q9Y4K4 (MAP4K5) , Q9UM73 (ALK) , O14965 (AURKA) , P23443 (RPS6KB1) , Q13237 (PRKG2) , P05771 (PRKCB) , P51812 (RPS6KA3) , Q15831 (STK11) , Q9UBS0 (RPS6KB2) , P49841 (GSK3B) , P24723 (PRKCH) , P17612 (PRKACA) , O94806 (PRKD3) , Q05655 (PRKCD) , P31749 (AKT1) , P17252 (PRKCA) , Q15418 (RPS6KA1) , Q9Y243 (AKT3) , Q96BR1 (SGK3)
S13 Phosphorylation
K15 Ubiquitination
S21 Phosphorylation
S25 Phosphorylation
K27 Methylation
K27 Ubiquitination
S35 Phosphorylation
K36 Ubiquitination
T43 Phosphorylation P27361 (MAPK3) , P28482 (MAPK1)
S66 Phosphorylation
Y71 Phosphorylation
K85 Ubiquitination
K103 Ubiquitination
Y114 Phosphorylation
Y117 Phosphorylation
S147 Phosphorylation Q05513 (PRKCZ)
K183 Ubiquitination
K197 Ubiquitination
S203 Phosphorylation
K205 Acetylation
K205 Ubiquitination
S215 Phosphorylation
Y216 Phosphorylation P49841 (GSK3B) , Q02750 (MAP2K1)
S219 Phosphorylation
Y221 Phosphorylation
Y222 Phosphorylation
T275 Phosphorylation
T277 Phosphorylation
Y288 Phosphorylation
K292 Sumoylation
K292 Ubiquitination
K297 Ubiquitination
C317 S-Nitrosylation
K349 Ubiquitination
S389 Phosphorylation Q16539 (MAPK14)
T390 Phosphorylation Q16539 (MAPK14)
T392 Phosphorylation
T395 Phosphorylation
T402 Phosphorylation
S417 Phosphorylation
T420 Phosphorylation

PTMs - P49841 As Enzyme

Substrate Site Source
E9PAV3 (NACA) T2022 Uniprot
O00327 (ARNTL) S17 Uniprot
O00327 (ARNTL) T21 Uniprot
O00429 (DNM1L) S40 Uniprot
O00429 (DNM1L) S44 Uniprot
O00429 (DNM1L) S693 Uniprot
O15169 (AXIN1) T481 Uniprot
O15169 (AXIN1) S486 Uniprot
O15169-2 (AXIN1) S614 Uniprot
O15294 (OGT) S3 Uniprot
O15294 (OGT) S4 Uniprot
O15516 (CLOCK) S427 Uniprot
O43602-2 (DCX) S327 Uniprot
O43602 (DCX) S332 Uniprot
O43623 (SNAI2) S92 Uniprot
O43623 (SNAI2) S96 Uniprot
O43623 (SNAI2) S100 Uniprot
O43623 (SNAI2) S104 Uniprot
O60341 (KDM1A) S683 Uniprot
O60346 (PHLPP1) S1359 Uniprot
O60346 (PHLPP1) T1363 Uniprot
O60346 (PHLPP1) S1379 Uniprot
O60346 (PHLPP1) S1381 Uniprot
O60716-6 (CTNND1) S252 Uniprot
O60716-6 (CTNND1) T310 Uniprot
O75030-10 (MITF) S292 Uniprot
O75030-9 (MITF) S298 Uniprot
O75030-8 (MITF) S383 Uniprot
O75030-9 (MITF) S397 Uniprot
O75030-6 (MITF) S398 Uniprot
O75030-2 (MITF) S399 Uniprot
O75030-9 (MITF) S401 Uniprot
O75030-9 (MITF) S405 Uniprot
O75122 (CLASP2) S499 Uniprot
O75122 (CLASP2) S503 Uniprot
O75122 (CLASP2) S507 Uniprot
O75122 (CLASP2) S533 Uniprot
O75122 (CLASP2) S537 Uniprot
O75581 (LRP6) S1490 Uniprot
O75581 (LRP6) T1572 Uniprot
O75581 (LRP6) S1607 Uniprot
O75925 (PIAS1) S17 Uniprot
O75952-5 (CABYR) T53 Uniprot
O75952-5 (CABYR) S57 Uniprot
O75952-2 (CABYR) T133 Uniprot
O75952-2 (CABYR) S137 Uniprot
O75952 (CABYR) T151 Uniprot
O75952-4 (CABYR) S155 Uniprot
O95271 (TNKS) S978 Uniprot
O95271 (TNKS) T982 Uniprot
O95271 (TNKS) S987 Uniprot
O95271 (TNKS) S991 Uniprot
O95863 (SNAI1) S92 Uniprot
O95863 (SNAI1) S96 Uniprot
O95863 (SNAI1) S100 Uniprot
O95863 (SNAI1) S104 Uniprot
O95863 (SNAI1) S107 Uniprot
O95863 (SNAI1) S111 Uniprot
O95863 (SNAI1) S115 Uniprot
O95863 (SNAI1) S119 Uniprot
P01106 (MYC) T58 Uniprot
P01106-2 (MYC) T73 Uniprot
P01112 (HRAS) T144 Uniprot
P01112 (HRAS) T148 Uniprot
P03372 (ESR1) S102 Uniprot
P03372 (ESR1) S104 Uniprot
P03372 (ESR1) S106 Uniprot
P03372 (ESR1) S118 Uniprot
P04150 (NR3C1) S404 Uniprot
P04637-1 (TP53) S33 Uniprot
P04637 (TP53) S376 Uniprot
P05067-4 (APP) T668 Uniprot
P05067-8 (APP) T724 Uniprot
P05067-1 (APP) T743 Uniprot
P05412 (JUN) T239 Uniprot
P05412 (JUN) S243 Uniprot
P06401-2 (PGR) S390 Uniprot
P08047 (SP1) S728 Uniprot
P08047 (SP1) S732 Uniprot
P10070 (GLI2) S820 Uniprot
P10070 (GLI2) S832 Uniprot
P10070 (GLI2) S863 Uniprot
P10636-8 (MAPT) S46 Uniprot
P10636-8 (MAPT) T50 Uniprot
P10636-2 (MAPT) T123 Uniprot
P10636-6 (MAPT) S126 Uniprot
P10636-6 (MAPT) S137 Uniprot
P10636-2 (MAPT) S140 Uniprot
P10636-2 (MAPT) S141 Uniprot
P10636-2 (MAPT) S144 Uniprot
P10636-6 (MAPT) T147 Uniprot
P10636-2 (MAPT) S150 Uniprot
P10636-8 (MAPT) T153 Uniprot
P10636-6 (MAPT) T154 Uniprot
P10636-2 (MAPT) T159 Uniprot
P10636-2 (MAPT) T173 Uniprot
P10636-8 (MAPT) T175 Uniprot
P10636-8 (MAPT) T181 Uniprot
P10636-8 (MAPT) S195 Uniprot
P10636-8 (MAPT) S198 Uniprot
P10636-8 (MAPT) S199 Uniprot
P10636-8 (MAPT) S202 Uniprot
P10636-6 (MAPT) S204 Uniprot
P10636-8 (MAPT) T205 Uniprot
P10636-8 (MAPT) S208 Uniprot
P10636-8 (MAPT) S210 Uniprot
P10636-8 (MAPT) T212 Uniprot
P10636-8 (MAPT) S214 Uniprot
P10636-8 (MAPT) T217 Uniprot
P10636-8 (MAPT) T231 Uniprot
P10636-8 (MAPT) S235 Uniprot
P10636-8 (MAPT) S262 Uniprot
P10636-2 (MAPT) S307 Uniprot
P10636-2 (MAPT) S311 Uniprot
P10636-2 (MAPT) S315 Uniprot
P10636-2 (MAPT) S324 Uniprot
P10636-6 (MAPT) S338 Uniprot
P10636-6 (MAPT) S342 Uniprot
P10636-6 (MAPT) S346 Uniprot
P10636-8 (MAPT) S396 Uniprot
P10636 (MAPT) S400 Uniprot
P10636-8 (MAPT) S404 Uniprot
P10636-8 (MAPT) S409 Uniprot
P10636-8 (MAPT) S413 Uniprot
P10636-8 (MAPT) S422 Uniprot
P10636 (MAPT) T498 Uniprot
P10636 (MAPT) S512 Uniprot
P10636 (MAPT) S515 Uniprot
P10636 (MAPT) S516 Uniprot
P10636 (MAPT) S519 Uniprot
P10636 (MAPT) T522 Uniprot
P10636 (MAPT) T529 Uniprot
P10636 (MAPT) S531 Uniprot
P10636 (MAPT) T534 Uniprot
P10636 (MAPT) T548 Uniprot
P10636 (MAPT) S579 Uniprot
P10636 (MAPT) S713 Uniprot
P10636 (MAPT) S717 Uniprot
P10636 (MAPT) S721 Uniprot
P11388 (TOP2A) S1361 Uniprot
P12036 (NEFH) S503 Uniprot
P12524 (MYCL) S38 Uniprot
P12524 (MYCL) S42 Uniprot
P12830-1 (CDH1) S847 Uniprot
P13807 (GYS1) S641 Uniprot
P13807 (GYS1) S645 Uniprot
P13807-1 (GYS1) S649 Uniprot
P13807-1 (GYS1) S653 Uniprot
P15924 (DSP) S2845 Uniprot
P15924 (DSP) S2849 Uniprot
P15941-7 (MUC1) S227 Uniprot
P15941-11 (MUC1) S236 Uniprot
P15941-8 (MUC1) S245 Uniprot
P15941 (MUC1) S1227 Uniprot
P16220-2 (CREB1) S115 Uniprot
P16220-1 (CREB1) S129 Uniprot
P16401 (HIST1H1B) T11 Uniprot
P16471 (PRLR) S349 Uniprot
P17275 (JUNB) S251 Uniprot
P17275 (JUNB) T255 Uniprot
P17676 (CEBPB) S223 Uniprot
P17676 (CEBPB) T226 Uniprot
P17676 (CEBPB) S231 Uniprot
P19838-2 (NFKB1) S900 Uniprot
P19838-2 (NFKB1) S904 Uniprot
P19838-2 (NFKB1) S908 Uniprot
P20393 (NR1D1) S55 Uniprot
P20393 (NR1D1) S59 Uniprot
P22670 (RFX1) S120 Uniprot
P22670 (RFX1) T124 Uniprot
P23246 (SFPQ) T687 Uniprot
P23760 (PAX3) S201 Uniprot
P24385 (CCND1) T286 Uniprot
P24385 (CCND1) T288 Uniprot
P24864 (CCNE1) S73 Uniprot
P24864 (CCNE1) T77 Uniprot
P24864 (CCNE1) T395 Uniprot
P25054 (APC) S1501 Uniprot
P25054 (APC) S1503 Uniprot
P30279 (CCND2) T280 Uniprot
P30281 (CCND3) T283 Uniprot
P30291 (WEE1) S211 Uniprot
P30304 (CDC25A) S76 Uniprot
P33076 (CIITA) S373 Uniprot
P35222 (CTNNB1) S33 Uniprot
P35222 (CTNNB1) S37 Uniprot
P35222 (CTNNB1) T41 Uniprot
P35612 (ADD2) S613 Uniprot
P35612 (ADD2) S693 Uniprot
P36956 (SREBF1) T426 Uniprot
P36956 (SREBF1) S430 Uniprot
P36956 (SREBF1) S434 Uniprot
P37840 (SNCA) S129 Uniprot
P38936 (CDKN1A) T57 Uniprot
P38936 (CDKN1A) S114 Uniprot
P40337 (VHL) S68 Uniprot
P41236 (PPP1R2) T73 Uniprot
P49715-1 (CEBPA) T226 Uniprot
P49715-1 (CEBPA) T230 Uniprot
P49716 (CEBPD) S167 Uniprot
P49768 (PSEN1) S353 Uniprot
P49768 (PSEN1) S357 Uniprot
P49841 (GSK3B) S9 Uniprot
P49841 (GSK3B) Y216 Uniprot
P50219 (MNX1) S77 Uniprot
P50219 (MNX1) S79 Uniprot
P50895 (BCAM) S596 Uniprot
P53396-1 (ACLY) T447 Uniprot
P53396-1 (ACLY) S451 Uniprot
P53805-4 (RCAN1) S28 Uniprot
P53805-2 (RCAN1) S108 Uniprot
P53805-1 (RCAN1) S163 Uniprot
P54132 (BLM) T171 Uniprot
P54252 (ATXN3) S256 Uniprot
P56524 (HDAC4) S298 Uniprot
P56524 (HDAC4) S302 Uniprot
P57059 (SIK1) T182 Uniprot
P58012 (FOXL2) S33 Uniprot
P60484 (PTEN) S362 Uniprot
P60484 (PTEN) T366 Uniprot
P84022 (SMAD3) T66 Uniprot
Q00613 (HSF1) S303 Uniprot
Q00653 (NFKB2) S222 Uniprot
Q00653 (NFKB2) S707 Uniprot
Q00653 (NFKB2) S711 Uniprot
Q01094 (E2F1) S403 Uniprot
Q01094 (E2F1) T433 Uniprot
Q01201 (RELB) S573 Uniprot
Q01974 (ROR2) S864 Uniprot
Q02156 (PRKCE) S346 Uniprot
Q03060-16 (CREM) S83 Uniprot
Q04206 (RELA) S468 Uniprot
Q04721 (NOTCH2) T2068 Uniprot
Q04721 (NOTCH2) S2070 Uniprot
Q04721 (NOTCH2) T2074 Uniprot
Q04721 (NOTCH2) S2093 Uniprot
Q07812 (BAX) S163 Uniprot
Q07817 (BCL2L1) S62 Uniprot
Q07820-2 (MCL1) S159 Uniprot
Q07820-1 (MCL1) T163 Uniprot
Q12778 (FOXO1) S325 Uniprot
Q13131 (PRKAA1) S486 Uniprot
Q13131 (PRKAA1) T490 Uniprot
Q13144 (EIF2B5) S535 Uniprot
Q13144 (EIF2B5) S540 Uniprot
Q13144 (EIF2B5) S544 Uniprot
Q13541 (EIF4EBP1) T37 Uniprot
Q13541 (EIF4EBP1) T46 Uniprot
Q13887 (KLF5) S303 Uniprot
Q14103-3 (HNRNPD) S83 Uniprot
Q14194 (CRMP1) T509 Uniprot
Q14194 (CRMP1) T514 Uniprot
Q14194 (CRMP1) S518 Uniprot
Q14195 (DPYSL3) T509 Uniprot
Q14195 (DPYSL3) T514 Uniprot
Q14195 (DPYSL3) S518 Uniprot
Q14494 (NFE2L1) S379 Uniprot
Q14896 (MYBPC3) S133 Uniprot
Q15208 (STK38) S6 Uniprot
Q15208 (STK38) T7 Uniprot
Q15746 (MYLK) S1776 Uniprot
Q15797 (SMAD1) T202 Uniprot
Q15853 (USF2) S155 Uniprot
Q15853 (USF2) T230 Uniprot
Q15910 (EZH2) S363 Uniprot
Q15910 (EZH2) T367 Uniprot
Q16236 (NFE2L2) S344 Uniprot
Q16236 (NFE2L2) S347 Uniprot
Q16555 (DPYSL2) T509 Uniprot
Q16555-1 (DPYSL2) T514 Uniprot
Q16555 (DPYSL2) S518 Uniprot
Q6PGQ7 (BORA) S274 Uniprot
Q6PGQ7 (BORA) S278 Uniprot
Q6R327 (RICTOR) S1235 Uniprot
Q6R327 (RICTOR) T1695 Uniprot
Q7KZI7 (MARK2) S212 Uniprot
Q8IZQ8 (MYOCD) S451 Uniprot
Q8IZQ8-1 (MYOCD) S455 Uniprot
Q8IZQ8 (MYOCD) S459 Uniprot
Q8IZQ8 (MYOCD) S463 Uniprot
Q8IZQ8 (MYOCD) S626 Uniprot
Q8IZQ8-1 (MYOCD) S630 Uniprot
Q8IZQ8 (MYOCD) S634 Uniprot
Q8IZQ8 (MYOCD) S638 Uniprot
Q8N122 (RPTOR) S722 Uniprot
Q8N122 (RPTOR) S792 Uniprot
Q8N122 (RPTOR) S859 Uniprot
Q8N122 (RPTOR) S863 Uniprot
Q8N122 (RPTOR) S877 Uniprot
Q8NHW3 (MAFA) S49 Uniprot
Q8NHW3 (MAFA) T53 Uniprot
Q8NHW3 (MAFA) T57 Uniprot
Q8NHW3 (MAFA) S61 Uniprot
Q92597 (NDRG1) S342 Uniprot
Q92597 (NDRG1) S352 Uniprot
Q92597 (NDRG1) S362 Uniprot
Q92837 (FRAT1) S188 Uniprot
Q92993 (KAT5) S86 Uniprot
Q92993 (KAT5) S90 Uniprot
Q96F46 (IL17RA) T780 Uniprot
Q96G01-1 (BICD1) S585 Uniprot
Q96G01-4 (BICD1) T597 Uniprot
Q96R06 (SPAG5) T111 Uniprot
Q96R06 (SPAG5) T937 Uniprot
Q96R06 (SPAG5) S974 Uniprot
Q96R06 (SPAG5) T978 Uniprot
Q96RR4 (CAMKK2) S129 Uniprot
Q96RR4 (CAMKK2) S133 Uniprot
Q96RR4 (CAMKK2) S137 Uniprot
Q99626 (CDX2) S283 Uniprot
Q9BYG3 (NIFK) S230 Uniprot
Q9BYG3 (NIFK) T234 Uniprot
Q9H0B6 (KLC2) S608 Uniprot
Q9H0Z9 (RBM38) S195 Uniprot
Q9HB09 (BCL2L12) S156 Uniprot
Q9NP62 (GCM1) S322 Uniprot
Q9NQX3 (GPHN) S270 Uniprot
Q9NRD5 (PICK1) S342 Uniprot
Q9NRD5 (PICK1) S415 Uniprot
Q9NRR4 (DROSHA) S300 Uniprot
Q9NRR4 (DROSHA) S302 Uniprot
Q9NS23-2 (RASSF1) S175 Uniprot
Q9NS23-2 (RASSF1) S178 Uniprot
Q9NS23-2 (RASSF1) S179 Uniprot
Q9NYF8 (BCLAF1) S531 Uniprot
Q9UBN7 (HDAC6) S22 Uniprot
Q9UKA4 (AKAP11) T1136 Uniprot
Q9UKA4 (AKAP11) T1140 Uniprot
Q9UKT5 (FBXO4) S12 Uniprot
Q9UMX1 (SUFU) S342 Uniprot
Q9UQB3 (CTNND2) T1056 Uniprot
Q9Y6H5 (SNCAIP) S556 Uniprot

Research Backgrounds


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 (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. 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.


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. 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.

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.

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionSubcellular location
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.

Subunit Structure:

Monomer. Interacts with ARRB2, DISC1 and ZBED3 (By similarity). Interacts with CABYR, MMP2, MUC1, NIN and PRUNE1. Interacts with AXIN1; the interaction mediates hyperphosphorylation of CTNNB1 leading to its ubiquitination and destruction. Interacts with and phosphorylates SNAI1. Interacts with DNM1L (via a C-terminal domain). Found in a complex composed of MACF1, APC, AXIN1, CTNNB1 and GSK3B (By similarity). Interacts with SGK3. Interacts with DAB2IP (via C2 domain); the interaction stimulates GSK3B kinase activation. Interacts (via C2 domain) with PPP2CA. Interacts with the CLOCK-ARNTL/BMAL1 heterodimer. Interacts with the ARNTL/BMAL1. Interacts with CTNND2. Interacts with NCYM. The complex composed, at least, of APC, CTNNB1 and GSK3B interacts with JPT1; the interaction requires the inactive form of GSK3B (phosphorylated at 'Ser-9'). Forms a complex composed of PRKAR2A or PRKAR2B, GSK3B and GSKIP through GSKIP interaction; facilitates PKA-induced phosphorylation and regulates GSK3B activity. Interacts with GSKIP. Interacts with GID8. Interacts with PIWIL2 (By similarity). Interacts with LMBR1L. Interacts with DDX3X. Interacts with BIRC2. Interacts with TNFRSF10B; TNFRSF10B stimulation inhibits GSK3B kinase activity.


Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family. GSK-3 subfamily.

Research Fields

· Cellular Processes > Cell growth and death > Cell cycle.   (View pathway)

· Cellular Processes > Cellular community - eukaryotes > Focal adhesion.   (View pathway)

· Cellular Processes > Cellular community - eukaryotes > Signaling pathways regulating pluripotency of stem cells.   (View pathway)

· Environmental Information Processing > Signal transduction > ErbB signaling pathway.   (View pathway)

· Environmental Information Processing > Signal transduction > mTOR signaling pathway.   (View pathway)

· Environmental Information Processing > Signal transduction > PI3K-Akt signaling pathway.   (View pathway)

· Environmental Information Processing > Signal transduction > Wnt signaling pathway.   (View pathway)

· Environmental Information Processing > Signal transduction > Hedgehog signaling pathway.   (View pathway)

· Environmental Information Processing > Signal transduction > Hippo signaling pathway.   (View pathway)

· Human Diseases > Drug resistance: Antineoplastic > EGFR tyrosine kinase inhibitor resistance.

· Human Diseases > Endocrine and metabolic diseases > Insulin resistance.

· Human Diseases > Endocrine and metabolic diseases > Non-alcoholic fatty liver disease (NAFLD).

· Human Diseases > Neurodegenerative diseases > Alzheimer's disease.

· Human Diseases > Infectious diseases: Viral > Hepatitis C.

· Human Diseases > Infectious diseases: Viral > Measles.

· Human Diseases > Infectious diseases: Viral > Influenza A.

· Human Diseases > Infectious diseases: Viral > Human papillomavirus infection.

· Human Diseases > Infectious diseases: Viral > HTLV-I infection.

· Human Diseases > Infectious diseases: Viral > Epstein-Barr virus infection.

· Human Diseases > Cancers: Overview > Pathways in cancer.   (View pathway)

· Human Diseases > Cancers: Specific types > Colorectal cancer.   (View pathway)

· Human Diseases > Cancers: Specific types > Endometrial cancer.   (View pathway)

· Human Diseases > Cancers: Specific types > Prostate cancer.   (View pathway)

· Human Diseases > Cancers: Specific types > Basal cell carcinoma.   (View pathway)

· Human Diseases > Cancers: Specific types > Breast cancer.   (View pathway)

· Human Diseases > Cancers: Specific types > Hepatocellular carcinoma.   (View pathway)

· Human Diseases > Cancers: Specific types > Gastric cancer.   (View pathway)

· Organismal Systems > Immune system > Chemokine signaling pathway.   (View pathway)

· Organismal Systems > Development > Axon guidance.   (View pathway)

· Organismal Systems > Immune system > IL-17 signaling pathway.   (View pathway)

· Organismal Systems > Immune system > T cell receptor signaling pathway.   (View pathway)

· Organismal Systems > Immune system > B cell receptor signaling pathway.   (View pathway)

· Organismal Systems > Nervous system > Neurotrophin signaling pathway.   (View pathway)

· Organismal Systems > Nervous system > Dopaminergic synapse.

· Organismal Systems > Endocrine system > Insulin signaling pathway.   (View pathway)

· Organismal Systems > Endocrine system > Melanogenesis.

· Organismal Systems > Endocrine system > Prolactin signaling pathway.   (View pathway)

· Organismal Systems > Endocrine system > Thyroid hormone signaling pathway.   (View pathway)


1). Polysaccharide from Flammulina velutipes residues protects mice from Pb poisoning by activating Akt/GSK3β/Nrf-2/HO-1 signaling pathway and modulating gut microbiota. International Journal of Biological Macromolecules, 2023 (PubMed: 36610568) [IF=8.2]

2). GSK-3β-dependent Nrf2 antioxidant response modulates ferroptosis of lens epithelial cells in age-related cataract. Free Radical Biology and Medicine, 2023 (PubMed: 37156294) [IF=7.4]

3). Mitofusin2 Promotes β Cell Maturation from Mouse Embryonic Stem Cells via Sirt3/Idh2 Activation. Stem Cells International, 2022 (PubMed: 35386849) [IF=4.3]

4). Conditional knockout of ITGB4 in bronchial epithelial cells directs bronchopulmonary dysplasia. Research Square, 2022

Application: WB    Species: Mouse    Sample:

Figure.8. The effects of ITGB4 deletion on FAK/GSK3β/SOX2 pathway in mice.(A) The immunohistochemical staining of FAK, phospho-FAK, GSK3β, phospho-GSK3β and SOX2 at P28 (B) Western blotting detection of the expression of ITGB4、FAk、phospho-FAK、GSK3β、phospho-GSK3β、SOX2 at P28. (C) Quantification of western blotting

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