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|Application ||WB, IHC-P, E|
|Calculated MW||46744 Da|
|Other Names||Glycogen synthase kinase-3 beta, GSK-3 beta, Serine/threonine-protein kinase GSK3B, GSK3B|
|Target/Specificity||This GSK3B Antibody is generated from rabbits immunized with a KLH conjugated synthetic phosphopeptide corresponding to amino acid residues surrounding S21/29 of human GSK3B.|
|Format||Purified polyclonal antibody supplied in PBS with 0.09% (W/V) sodium azide. This antibody is purified through a protein A column, followed by peptide affinity purification.|
|Storage||Maintain refrigerated at 2-8°C for up to 2 weeks. For long term storage store at -20°C in small aliquots to prevent freeze-thaw cycles.|
|Precautions||Bi-Phospho-GSK3B(S21/29) Antibody is for research use only and not for use in diagnostic or therapeutic procedures.|
|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 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 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, 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).|
|Cellular Location||Cytoplasm. Nucleus. Cell membrane. Note=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)|
|Tissue Location||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|
Provided below are standard protocols that you may find useful for product applications.
Glycogen synthase kinase-3 (GSK3) is a proline-directed serine-threonine kinase that was initially identified as a phosphorylating and inactivating glycogen synthase. Two isoforms, alpha (GSK3A) and beta, show a high degree of amino acid homology. GSK3B is involved in energy metabolism, neuronal cell development, and body pattern formation.
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Liao, X., et al., Endocrinology 145(6):2941-2949 (2004).
Salas, T.R., et al., J. Biol. Chem. 279(18):19191-19200 (2004).
Takahashi-Yanaga, F., et al., Biochem. Biophys. Res. Commun. 316(2):411-415 (2004).