Phospho-GSK3A/GSK3B (Y216 + Y279) Recombinant Monoclonal Antibody

Code CSB-RA009962A216phHU
Size US$210
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Image
  • IHC image of CSB-RA009962A216phHU diluted at 1:100 and staining in paraffin-embedded human pancreatic tissue performed on a Leica BondTM system. After dewaxing and hydration, antigen retrieval was mediated by high pressure in a citrate buffer (pH 6.0). Section was blocked with 10% normal goat serum 30min at RT. Then primary antibody (1% BSA) was incubated at 4℃ overnight. The primary is detected by a biotinylated secondary antibody and visualized using an HRP conjugated SP system.
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Product Details

Uniprot No.
Target Names
GSK3A
Alternative Names
DKFZp686D0638 antibody; Glycogen synthase kinase 3 alpha antibody; Glycogen synthase kinase-3 alpha antibody; GSK 3 alpha antibody; GSK 3A antibody; GSK-3 alpha antibody; Gsk3a antibody; GSK3A_HUMAN antibody; GSK3alpha antibody; Serine/threonine protein kinase GSK3A antibody
Species Reactivity
Human
Immunogen
A synthesized peptide derived from Human Phospho-GSK3A/GSK3B (Y216 + Y279)
Immunogen Species
Homo sapiens (Human)
Conjugate
Non-conjugated
Clonality
Monoclonal
Isotype
Rabbit IgG
Clone No.
4A5
Purification Method
Affinity-chromatography
Concentration
It differs from different batches. Please contact us to confirm it.
Buffer
Rabbit IgG in phosphate buffered saline , pH 7.4, 150mM NaCl, 0.02% sodium azide and 50% glycerol.
Form
Liquid
Tested Applications
ELISA, IHC
Recommended Dilution
Application Recommended Dilution
IHC 1:50-1:200
Troubleshooting and FAQs
Storage
Upon receipt, store at -20°C or -80°C. Avoid repeated freeze.
Lead Time
Basically, we can dispatch the products out in 1-3 working days after receiving your orders. Delivery time maybe differs from different purchasing way or location, please kindly consult your local distributors for specific delivery time.
Description

Phospho-GSK3A/GSK3B (Y216 + Y279) antibody CSB-RA009962A216phHU is a recombinant monoclonal antibody belonging to rabbit IgG. Its production procedures include: the acquisition of the anti-GSK3 Beta-pY216 + GSK3 Alpha-pY279 monoclonal antibody using the synthesized peptide derived from the human phospho-GSK3A/GSK3B (Y216 + Y279) immunizes animals; the determination of DNA sequence of the monoclonal antibody; the clone of the DNA sequence into the plasmid and subsequent transfection into cell lines for expression. This phospho-GSK3A/GSK3B (Y216 + Y279) antibody underwent purification using affinity-chromatography. It has been tested in ELISA and IHC. It is reactive with the human phospho-GSK3A/GSK3B (Y216 + Y279) protein.

All eukaryotes have GSK3, which is a versatile serine/threonine kinase. GSK3 is engaged in a wide range of cellular functions, from glycogen metabolism to cell cycle regulation and proliferation, and is a crucial regulator of numerous signaling pathways, including cellular responses to Wnt, receptor tyrosine kinases, and G protein-coupled receptors. GSK3α and GSK3β are two GSK-3 isoforms. GSK3 kinase activity is activated by phosphorylation on tyrosine residues (GSK3 Y279 and GSK3 Y216).

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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), CTNNB1/beta-catenin, APC and AXIN1. Requires primed phosphorylation of the majority of its substrates. Contributes to insulin regulation of glycogen synthesis by phosphorylating and inhibiting GYS1 activity and hence glycogen synthesis. Regulates glycogen metabolism in liver, but not in muscle. May also mediate the development of insulin resistance by regulating activation of transcription factors. In Wnt signaling, regulates the level and transcriptional activity of nuclear CTNNB1/beta-catenin. Facilitates amyloid precursor protein (APP) processing and the generation of APP-derived amyloid plaques found in Alzheimer disease. May be involved in the regulation of replication in pancreatic beta-cells. Is necessary for the establishment of neuronal polarity and axon outgrowth. Through phosphorylation of the anti-apoptotic protein MCL1, may control cell apoptosis in response to growth factors deprivation. 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
  1. GSK-3a and GSK-3b play pivotal roles in hepatocellular carcinoma. (Review) PMID: 28619606
  2. he combined action of CHIR99021 and forskolin markedly delayed neurological deficits and significantly reduced the tumor volume. We suggest that reprogramming technology may be a potential treatment strategy replacing the therapeutic paradigm of traditional treatment of malignant glioma, and a combination molecule comprising a GSK3 inhibitor and a cAMP inducer could be the next generation of anticancer drugs. PMID: 29161257
  3. Using integrated analysis of genome-wide short hairpin RNA (shRNA) screening data in combination with genome-wide gene expression data, the study identified GSK3 as one of the key factors in p53-mediated apoptosis in human lung cancer cells. PMID: 28662516
  4. demonstrated that GSK-3alpha is regulated by CREB in lung cancer and is required for the cell viability. These findings implicate CREB-GSK-3alpha axis as a novel therapeutic target for lung cancer treatment PMID: 27049759
  5. GSK3 acts through APC motifs R2 and B to regulate APC:Axin interactions, promoting high-throughput of betacatenin to destruction. PMID: 26393419
  6. reveals that GSK-3alpha- and GSK-3beta-regulated pathways can be responsible for stepwise transition to myelodysplastic syndromes and subsequent acute myeloid leukemia PMID: 26766591
  7. CHP3 functions as a novel negative regulator of cardiomyocyte hypertrophy via inhibition of GSK3alpha/beta phosphorylation. PMID: 25935310
  8. Elevated GSK3 protein kinase activity is associated with non-small cell lung carcinoma PMID: 25486534
  9. GSK3A is redundant with GSK3B in regulating drug-resistance and chemotherapy-induced necroptosis PMID: 24984063
  10. ER stress-PERK-GSK3alpha/beta signaling promotes proatherogenic macrophage lipid accumulation PMID: 25183803
  11. glycogen synthase kinase 3 alpha and beta activity is increased in foetal membranes after term and preterm labour PMID: 25550525
  12. TRAIL-induced apoptosis in pancreatic ductal adenocarcinoma cell lines is enhanced by pharmacological inhibition of glycogen synthase kinase-3 (GSK-3) or by shRNA-mediated depletion of either GSK-3alpha or GSK-3beta. PMID: 24675460
  13. Data indicate that autophagy inhibition promotes glycogen synthase kinase-(GSK3) inhibition-induced apoptosis. PMID: 25561726
  14. PtpA has a role in promoting anti-apoptotic activity of protein-dependent dephosphorylation of host GSK3alpha PMID: 25187516
  15. Protein Kinase B-dependent phosphorylation of glycogen synthase kinase GSK-3 contributes to the pro-fibrotic signaling leading to renal tissue fibrosis in obstructive nephropathy PMID: 24685987
  16. This review highlights the emerging role of GSK3alpha in Alzheimer's disease which has been largely overlooked in favor of GSK3beta. PMID: 24254703
  17. In lipopolysaccharide-stimulated human neutrophils, GSK-3-alpha inhibitors mimicked the effect of LiCl, by potentiating TNF-alpha release after 4 h. GSK-3 inhibition prolongs activation of the p38/MNK1/eIF4E pathway of mRNA translation. PMID: 24803542
  18. JNK and GSK3 especially are potential signaling molecules regulating BMP-induced osteoblastic human mesenchymal stem cells differentiation. PMID: 24060635
  19. GSK-3 expression and regulation in human neutrophils, was investigated. PMID: 24035907
  20. this studydemonstrated abundant levels of the critical negative cell-cycle regulators, p27(Kip1), its phosphorylated form, p-p27(S10), p18Ink4c, and GSK-3, in beta-cells of both adult human and mouse pancreatic islets, which contribute to maintenance of beta-cell quiescence. PMID: 23896637
  21. The involvement of GSK-3 in several key pathophysiological pathways leading to AD and neurodegenerative diseases has placed this enzyme in a central position in this disorder. PMID: 23621307
  22. GSK3alpha, GSK3beta, and MAPK13 were found to be the most active tau kinases, phosphorylating tau at all four epitopes. PMID: 23798682
  23. Studies indicate the therapeutic potential of GSK-3 inhibitors for treatment of neurodegenerative and behavior disorders. PMID: 23369789
  24. Lower phosphorylation levels of GSK3A is associated with poor treatment response in rectal cancer. PMID: 22658458
  25. Findings suggest that inhibiton of Bcl-2, Bcl-xL and PI3K, and release of Bim from Bcl-2/Bcl-xL and GSK3alpha/beta culminating in Bax/Bak activation and apoptosis. PMID: 23243017
  26. GSK-3 may play a crucial role in the inflammatory process in chronic rhinosinusitis with nasal polyps (CRSwNP). PMID: 23352529
  27. GSK-3alpha is more prevalent in low Gleason score tumors, where it might promote androgen-dependent proliferation by activating androgen receptor. PMID: 22539113
  28. glycogen synthase kinase-3 (GSK3), when deinhibited by default in cells deprived of growth factors, activates acetyltransferase TIP60 through phosphorylating TIP60-Ser86, which acetylates and stimulates the protein kinase ULK1, which is required for autophagy PMID: 22539723
  29. investigated whether GSK-3 activity is regulated by thymosin beta-4 (Tbeta4) and associated with Tbeta4-mediated migration in gastric cancer cells; expression of GSK-3alpha, beta-catenin and E-cadherin could be negatively regulated by Tbeta4 induced ERK phosphorylation; suggests that Tbeta4 could be a novel regulator to control Wnt signal pathway PMID: 22328534
  30. GSK3 inhibitor-BIO regulates proliferation of immortalized pancreatic mesenchymal stem cells PMID: 22384031
  31. GSK-3alpha has a role and is a target in human acute myeloid leukemia PMID: 22326953
  32. Glycogen synthase kinase (GSK)-3 promotes p70 ribosomal protein S6 kinase (p70S6K) activity and cell proliferation. PMID: 22065737
  33. Data show that p53 directly up-regulates microRNA-149* (miR-149*) that in turn targets glycogen synthase kinase-3alpha, resulting in increased expression of Mcl-1 and resistance to apoptosis in melanoma cells. PMID: 21896753
  34. GSK3 acts as a molecular brake on the signaling pathway, leading to TF expression in monocytes interacting with activated platelets PMID: 21320285
  35. The authors demonstrate that inhibition of GSK-3 dampens Bacillus anthracis edema toxin-induced maturation and migration processes of monocyte-derived dendritic cells. PMID: 21576335
  36. Overexpression of glycogen synthase kinase-3 alpha in ovarian carcinoma cells is associated with acquired paclitaxel resistance. PMID: 21436692
  37. Investigations with human tissues in this review strongly support the postulate that GSK3 has a pathological role in mood disorders and is likely a therapeutic target in mood disorder treatment. PMID: 20668436
  38. Data show that the effects of PI3K-Akt signalling on IL-10 responses were mediated at least in part by GSK3. PMID: 21255011
  39. in multiple myeloma cells GSK-3alpha and beta play distinct roles in cell survival and modulate the sensitivity to proteasome inhibitors PMID: 20920357
  40. Phosphorylation of proteins in the brain associated with Alzheimer's disease is altered in cortical tissue lacking transgenic glycogen synthase kinase-3alpha and -3ss. PMID: 20831597
  41. widely expressed throughout the hair follicles PMID: 19705135
  42. Glycogen synthase kinase (GSK3) plays a central role in promoting glucocorticoid-induced apoptosis. PMID: 20371704
  43. GSK-3 maintains the MLL leukemia stem cell transcriptional program by promoting the conditional association of CREB and its coactivators TORC and CBP with homedomain protein MEIS1, which in turn facilitates HOX-mediated transcription and transformation. PMID: 20541704
  44. study suggests that downstream signaling components of the PI3K/Akt pathway, GSK3 & cyclin D2 as well as the significant interaction between PTEN-PDK and between pAkt-pGSK3beta, are involved in the survival and proliferation of leiomyomas. PMID: 19464003
  45. the N termini of both GSK-3 isoforms were dispensable, whereas progressive C-terminal deletions resulted in protein misfolding exhibited by deficient activity, impaired ability to interact with Axin, and a loss of Tyr(279/216) phosphorylation PMID: 20080974
  46. Studies show that GSK-3 and Omi/HtrA2 synergistically cause annexin A2 cleavage and then cell cycle inhibition or apoptosis. PMID: 19656851
  47. immunoreactivity of IGF-I and GSK3a/b signaling pathways studied in ALS spinal cords and hippocampus with special reference to Kii and Guam ALS patients: in Japanese ALS patients, IGF-I expression was positively correlated with the clinical duration. PMID: 19323791
  48. improves insulin action and glucose metabolism in skeletal muscle PMID: 12086949
  49. GSK3alpha is a potential regulator of platelet function PMID: 14550568
  50. Data show that myotubes defective in glycogen synthase (GS) activity express insulin-responsive glycogen synthase kinase-3alpha, suggesting that failure of insulin to decrease GS phosphorylation involves abnormal activity of another kinase or phosphatase. PMID: 15194499

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

HGNC: 4616

OMIM: 606784

KEGG: hsa:2931

STRING: 9606.ENSP00000222330

UniGene: Hs.466828

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