Recombinant Human GSK3 beta protein

Specifications

Form

Liquid

Additional notes

Affinity purified

General info

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 : 11430833, PubMed : 12554650, PubMed : 14690523, PubMed : 16484495, PubMed : 1846781, PubMed : 20937854, PubMed : 9072970). 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 inhibition of its activity (By similarity). Phosphorylates SIK1 at 'Thr-182', leading to sustainment of its activity (PubMed : 18348280). Phosphorylates ZC3HAV1 which enhances its antiviral activity (PubMed : 22514281). Phosphorylates SNAI1, leading to its ubiquitination and proteasomal degradation (PubMed : 15448698, PubMed : 15647282, PubMed : 25827072, PubMed : 29059170). 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 BMAL1, CLOCK and PER2 (PubMed : 19946213, PubMed : 28903391). Phosphorylates FBXL2 at 'Thr-404' and primes it for ubiquitination by the SCF(FBXO3) complex and proteasomal degradation (By similarity). Phosphorylates CLOCK AT 'Ser-427' and targets it for proteasomal degradation (PubMed : 19946213). Phosphorylates 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 BMAL1 and PER2 expression (By similarity). Acts as a regulator of autophagy by mediating phosphorylation of KAT5/TIP60 under starvation conditions, activating KAT5/TIP60 acetyltransferase activity and promoting 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, stabilizing E2F1 and promoting its activity (PubMed : 17050006, PubMed : 28992046). Phosphorylates mTORC2 complex component RICTOR at 'Thr-1695' which facilitates FBXW7-mediated ubiquitination and subsequent degradation of RICTOR (PubMed : 25897075). Phosphorylates FXR1, promoting FXR1 ubiquitination by the SCF(FBXO4) complex and FXR1 degradation by the proteasome (By similarity). Phosphorylates interleukin-22 receptor subunit IL22RA1, preventing its proteasomal degradation (By similarity).

Sequence similarities

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

Post-translational modifications

Phosphorylated by AKT1 and ILK1. Upon insulin-mediated signaling, the activated PKB/AKT1 protein kinase phosphorylates and deactivates 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.. Palmitoylated. Palmitoylation by ZDHHC4 prevents AKT1-mediated phosphorylation.

Subcellular localisation

Nucleus