Glycogen synthase kinase 3beta (GSK-3Beta) is a Serine/Threonine protein kinase involved in insulin and wingless pathways (1-2). Originally identified as a regulator of glycogen synthase, it has been shown to regulate a diverse array of cellular functions. GSK-3Beta activity is downregulated by phosphorylation on Serine 9 by PKB, or activated by phosphorylation on Tyrosine 216. Once activated, the protein can phosphorylate p53, c-jun, heat shock factor-1 and cyclin D1 (3-4). It is also known to phosphorylate Tau in Alzheimer's disease. Additionally, increased GSK-3Beta protein levels are found in Alzheimer's disease brains).
Product Information
Format
Unpurified
Control
A431 cell lysate
Presentation
Rabbit Monoclonal in buffer containing glycerol, BSA, and sodium azide.
Applications
Application
Please note that this product will not be available for sale after March 15, 2015. Please select one of the other antibodies against this target. Detect GSK3 using this Anti-GSK3 Antibody, clone Y174,
Rabbit Monoclonal validated for use in Western Blotting, ICC, IHC(P).
Key Applications
Immunohistochemistry (Paraffin)
Western Blotting
Immunocytochemistry
Application Notes
Immunohistochemistry Analysis: A 1:100-250 dilution from a representative lot was used in human colon carcinoma tissue.
Immunocytochemistry Analysis: A 1:100-250 dilution from a representative lot was used in IC.
Biological Information
Immunogen
A synthetic peptide corresponding to the C-terminus of human GSK3.
Epitope
C-terminus
Clone
Y174
Host
Rabbit
Specificity
This antibody recognizes the C-terminus of GSK3. The antibody may detect splice isoform 2 based on sequence homology.
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. 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. CATALYTIC ACTIVITY:ATP + [tau protein] = ADP + [tau protein] phosphate.
ATP + a protein = ADP + a phosphoprotein. ENZYME REGULATION:Activated by phosphorylation at Tyr-216. In response to insulin, inhibited by phosphorylation at Ser-9 by PKB/AKT1 and RPS6KA3; phosphorylation at this site causes a conformational change, preventing access of substrates to the active site. Inhibited by lithium. SUBUNIT STRUCTURE:Monomer By similarity. Interacts with ARRB2 and DISC1 By similarity. Interacts with CABYR, MMP2, MUC1, NIN and PRUNE 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. 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 phosophorylated form to the cell membrane. TISSUE SPECIFICITY:Expressed in testis, thymus, prostate and ovary and weakly expressed in lung, brain and kidney. PTM: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. MISCELLANEOUS:Higher expression and activity of GSK3B are found in the skeletal muscle (vastus lateralis) of patients with type 2 diabetes (Ref.16). Several potent GSK3 (GSK3A and GSK3B) inhibitors have been identified and characterized in preclinical models for treatments of type 2 diabetes (Ref.44). SEQUENCE SIMILARITIES:Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family. GSK-3 subfamily.
Contains 1 protein kinase domain.
Product Usage Statements
Quality Assurance
Evaluated by Western Blotting in A431 cell lysate.
Western Blotting Analysis: 1:10,000 dilution of this antibody detected GSK3 in A431 cell lysate.
Usage Statement
Unless otherwise stated in our catalog or other company documentation accompanying the product(s), our products are intended for research use only and are not to be used for any other purpose, which includes but is not limited to, unauthorized commercial uses, in vitro diagnostic uses, ex vivo or in vivo therapeutic uses or any type of consumption or application to humans or animals.
Storage and Shipping Information
Storage Conditions
Stable for 1 year at -20ºC from date of receipt.
Handling Recommendations: Upon first thaw, and prior to removing cap, centrifuge the vial and gently mix the solution. Aliquot into microcentrifuge tubes and store at -20ºC. Avoid freeze/thaw cycles, which may damage IgG and affect product performance.
Note: Variability in freezer temperatures below -20°C may cause glycerol containing solutions to become frozen during storage. Note: Variability in freezer temperatures below -20°C may cause glycerol containing solutions to become frozen during storage.
Glycogen synthase kinase 3beta (GSK-3Beta) is a Serine/Threonine protein kinase involved in insulin and wingless pathways (1-2). Originally identified as a regulator of glycogen synthase, it has been shown to regulate a diverse array of cellular functions. GSK-3Beta activity is downregulated by phosphorylation on Serine 9 by PKB, or activated by phosphorylation on Tyrosine 216. Once activated, the protein can phosphorylate p53, c-jun, heat shock factor-1 and cyclin D1 (3-4). It is also known to phosphorylate Tau in Alzheimer's disease. Additionally, increased GSK-3Beta protein levels are found in Alzheimer's disease brains).
Product Information
Format
Unpurified
Control
A431 cell lysate
Presentation
Rabbit Monoclonal in buffer containing glycerol, BSA, and sodium azide.
Applications
Application
Please note that this product will not be available for sale after March 15, 2015. Please select one of the other antibodies against this target. Detect GSK3 using this Anti-GSK3 Antibody, clone Y174,
Rabbit Monoclonal validated for use in Western Blotting, ICC, IHC(P).
Key Applications
Immunohistochemistry (Paraffin)
Western Blotting
Immunocytochemistry
Application Notes
Immunohistochemistry Analysis: A 1:100-250 dilution from a representative lot was used in human colon carcinoma tissue.
Immunocytochemistry Analysis: A 1:100-250 dilution from a representative lot was used in IC.
Biological Information
Immunogen
A synthetic peptide corresponding to the C-terminus of human GSK3.
Epitope
C-terminus
Clone
Y174
Host
Rabbit
Specificity
This antibody recognizes the C-terminus of GSK3. The antibody may detect splice isoform 2 based on sequence homology.
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. 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. CATALYTIC ACTIVITY:ATP + [tau protein] = ADP + [tau protein] phosphate.
ATP + a protein = ADP + a phosphoprotein. ENZYME REGULATION:Activated by phosphorylation at Tyr-216. In response to insulin, inhibited by phosphorylation at Ser-9 by PKB/AKT1 and RPS6KA3; phosphorylation at this site causes a conformational change, preventing access of substrates to the active site. Inhibited by lithium. SUBUNIT STRUCTURE:Monomer By similarity. Interacts with ARRB2 and DISC1 By similarity. Interacts with CABYR, MMP2, MUC1, NIN and PRUNE 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. 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 phosophorylated form to the cell membrane. TISSUE SPECIFICITY:Expressed in testis, thymus, prostate and ovary and weakly expressed in lung, brain and kidney. PTM: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. MISCELLANEOUS:Higher expression and activity of GSK3B are found in the skeletal muscle (vastus lateralis) of patients with type 2 diabetes (Ref.16). Several potent GSK3 (GSK3A and GSK3B) inhibitors have been identified and characterized in preclinical models for treatments of type 2 diabetes (Ref.44). SEQUENCE SIMILARITIES:Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family. GSK-3 subfamily.
Contains 1 protein kinase domain.
Product Usage Statements
Quality Assurance
Evaluated by Western Blotting in A431 cell lysate.
Western Blotting Analysis: 1:10,000 dilution of this antibody detected GSK3 in A431 cell lysate.
Usage Statement
Unless otherwise stated in our catalog or other company documentation accompanying the product(s), our products are intended for research use only and are not to be used for any other purpose, which includes but is not limited to, unauthorized commercial uses, in vitro diagnostic uses, ex vivo or in vivo therapeutic uses or any type of consumption or application to humans or animals.
Storage and Shipping Information
Storage Conditions
Stable for 1 year at -20ºC from date of receipt.
Handling Recommendations: Upon first thaw, and prior to removing cap, centrifuge the vial and gently mix the solution. Aliquot into microcentrifuge tubes and store at -20ºC. Avoid freeze/thaw cycles, which may damage IgG and affect product performance.
Note: Variability in freezer temperatures below -20°C may cause glycerol containing solutions to become frozen during storage. Note: Variability in freezer temperatures below -20°C may cause glycerol containing solutions to become frozen during storage.
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