GSK3B Human, sf9

Glycogen synthase kinase-3 beta, sf9 Human Recombinant
Shipped with Ice Packs
In Stock

Description

Biochemical Activity

Kinase Function:

  • Phosphorylates serine/threonine residues in substrates primed by prior phosphorylation (e.g., SARS-CoV-2 nucleocapsid protein at S180/S184, S190/S194, and T198/S202) .

  • Specific Activity: ≥500 pmol/min·μg in kinase assays .

Regulatory Mechanisms:

  • Inhibition: Phosphorylation at Ser9 by upstream kinases (e.g., AKT) .

  • Activation: Autophosphorylation at Tyr216 or phosphorylation by Src/Fyn kinases .

Viral Pathogenesis

  • SARS-CoV-2 Replication:

    • Phosphorylates the nucleocapsid (N) protein, facilitating viral assembly. Inhibition by T-1686568 (IC50: 0.3 nM) reduces viral replication .

    • Key phosphorylation sites identified via mass spectrometry (Table 1) .

Table 1: GSK3β-Dependent Phosphorylation Sites in SARS-CoV-2 N Protein

Phosphosite PairPriming SiteFunctional Role
S180/S184S188Viral replication
S190/S194T198Nucleocapsid assembly
T198/S202S206RNA binding efficiency

Metabolic Regulation

  • Insulin Signaling:

    • Inhibits glycogen synthase (GYS1) in skeletal muscle, reducing glucose storage .

    • Global knockout models show improved glucose tolerance and insulin sensitivity .

  • Adipogenesis:

    • Phosphorylation at Thr356 by Dyrk1A kinase suppresses adipocyte differentiation .

Inhibitor Development

Therapeutic Candidates:

  • T-1686568: Reduces SARS-CoV-2 replication at nanomolar concentrations in human organoids .

  • CHIR98023: Enhances glycogen synthase activity in skeletal muscle without affecting glucose uptake .

Screening Outcomes:

  • 31% of GSK3β-focused inhibitors showed ≥50% efficacy against HCoV-229E .

  • High hit rate (8%) in SARS-CoV-2 antiviral screens .

Product Specs

Introduction
Glycogen synthase kinase 3 beta (GSK3B) is a critical serine/threonine kinase involved in various cellular processes, including energy metabolism, neuronal development, and body pattern formation. Genetic variations in the GSK3B gene have been linked to an increased risk of Parkinson's disease. Additionally, research using mice models suggests that elevated GSK3B expression may play a role in Alzheimer's disease development.
Description
GSK3B, produced using Sf9 insect cells and Baculovirus expression system, is a single, glycosylated polypeptide chain with a molecular weight of 47.5 kDa. This protein consists of 426 amino acids, spanning from position 1 to 420. It includes a 6-amino acid Histidine tag located at the C-terminus to facilitate purification. The purification process involves proprietary chromatographic techniques, ensuring high purity.
Physical Appearance
The product is a clear, colorless solution that has been sterilized through filtration.
Formulation
The GSK3B protein is provided in a solution with a concentration of 0.25 mg/ml. The solution is formulated with Phosphate Buffered Saline (pH 7.4) for stability, 0.5mM PMSF as a protease inhibitor, and 30% glycerol to prevent freezing during storage.
Stability
For short-term storage (2-4 weeks), the GSK3B protein solution can be stored at 4°C. For long-term storage, it is recommended to store the solution at -20°C. To further enhance long-term stability, consider adding a carrier protein such as 0.1% HSA or BSA. It is crucial to minimize freeze-thaw cycles to maintain protein integrity and activity.
Purity
The purity of GSK3B protein is greater than 90%, as determined by SDS-PAGE analysis, indicating a high level of purity.
Synonyms
Glycogen synthase kinase-3 beta, GSK-3 beta, Serine/threonine-protein kinase GSK3B.
Source
Sf9, Baculovirus cells.
Amino Acid Sequence
MSGRPRTTSF AESCKPVQQP SAFGSMKVSR DKDGSKVTTV VATPGQGPDR PQEVSYTDTK VIGNGSFGVV YQAKLCDSGE LVAIKKVLQD KRFKNRELQI MRKLDHCNIV RLRYFFYSSG EKKDEVYLNL VLDYVPETVY RVARHYSRAK QTLPVIYVKL YMYQLFRSLA YIHSFGICHR DIKPQNLLLD PDTAVLKLCD FGSAKQLVRG EPNVSYICSR YYRAPELIFG ATDYTSSIDV WSAGCVLAEL LLGQPIFPGD SGVDQLVEII KVLGTPTREQ IREMNPNYTE FKFPQIKAHP WTKVFRPRTP PEAIALCSRL LEYTPTARLT PLEACAHSFF DELRDPNVKL PNGRDTPALF NFTTQELSSN PPLATILIPP HARIQAAAST PTNATAASDA NTGDRGQTNN AASASASNST HHHHHH.

Product Science Overview

Introduction

Glycogen Synthase Kinase-3 Beta (GSK3β) is a serine/threonine protein kinase that plays a crucial role in various cellular processes. It was initially identified as the kinase responsible for phosphorylating and inhibiting glycogen synthase, an enzyme involved in glycogen synthesis . GSK3β is ubiquitously present in human tissues and is implicated in the regulation of several physiological processes, including glucose homeostasis, energy metabolism, and cell signaling .

Structure and Function

GSK3β is a constitutively active kinase, meaning it is active under normal physiological conditions without the need for additional activation signals . It is involved in the hormonal control of glucose homeostasis, Wnt signaling, and the regulation of transcription factors and microtubules . GSK3β phosphorylates a wide range of substrates, including glycogen synthase, beta-catenin, and various transcription factors .

In skeletal muscle, GSK3β contributes to the regulation of glycogen synthesis by phosphorylating and inhibiting glycogen synthase activity . This regulation is crucial for maintaining proper glucose levels in the body. Additionally, GSK3β is involved in the development of insulin resistance by regulating the activation of transcription factors .

Recombinant GSK3β in sf9 Cells

Recombinant GSK3β is often produced using the baculovirus expression system in sf9 insect cells. This system allows for the production of high-quality, biologically active proteins that are suitable for various research applications . The recombinant GSK3β expressed in sf9 cells is typically purified to high levels of purity and is used in studies related to enzyme activity, protein-protein interactions, and drug discovery .

Applications and Research

GSK3β is a target of interest in various research fields, including neurodegenerative diseases, cancer, and diabetes. In Alzheimer’s disease, GSK3β is involved in the phosphorylation of tau protein, which leads to the formation of neurofibrillary tangles, a hallmark of the disease . In cancer research, GSK3β is studied for its role in cell proliferation and survival, making it a potential target for therapeutic interventions .

Quick Inquiry

Personal Email Detected
Please use an institutional or corporate email address for inquiries. Personal email accounts ( such as Gmail, Yahoo, and Outlook) are not accepted. *
© Copyright 2024 Thebiotek. All Rights Reserved.