GSK3B

GSK3B is a serine-threonine kinase, belonging to the glycogen synthase kinase subfamily. It Contains 1 protein kinase domain, and is expressed in testis, thymus, prostate and ovary and weakly expressed in lung, brain and kidney. GSK3B is involved in energy metabolism, neuronal cell development, and body pattern formation. Polymorphisms in GSK3B gene have been implicated in modifying risk of Parkinson disease, and studies in mice show that overexpression of this gene may be relevant to the pathogenesis of Alzheimer disease. GSK3B participates in the Wnt signaling pathway. It is implicated in the hormonal control of several regulatory proteins including glycogen synthase, MYB and the transcription factor JUN. Phosphorylates JUN at sites proximal to its DNA-binding domain, thereby reducing its affinity for DNA. Phosphorylates MUC1 in breast cancer cells, and decreases the interaction of MUC1 with CTNNB1/beta-catenin. GSK3B also plays an important role in ERBB2-dependent stabilization of microtubules at the cell cortex.

GSK3B Related Areas

Enzyme>>Protein Kinase>>Intracellular Kinase>>GSK3B

Signal Transduction>>Protein Kinase>>Intracellular Kinase>>GSK3B

GSK3B Related Pathways

• Canonical (beta-Catenin-Dependent) Wnt Signaling

GSK3B Alternative Names

GSK3B, GSK3beta isoform [Homo sapiens]

Gsk3b, GSK-3, GSK-3beta, GSK3, 7330414F15Rik, 8430431H08Rik, C86142 [Mus musculus]

Summaries for GSK3B

Entrez Gene summary for GSK3B:

The protein encoded by GSK3B is a serine-threonine kinase, belonging to the glycogen synthase kinase subfamily. It is involved in energy metabolism, neuronal cell development, and body pattern formation. Polymorphisms in GSK3B have been implicated in modifying risk of Parkinson disease, and studies in mice show that overexpression of GSK3B may be relevant to the pathogenesis of Alzheimer disease. Alternatively spliced transcript variants encoding different isoforms have been found for GSK3B.

OMIM - description for GSK3B:

Glycogen synthase kinase-3 (GSK3) is a proline-directed serine-threonine kinase that was initially identified as a phosphorylating and inactivating glycogen synthase (see GYS1, 138570). Two isoforms, alpha (GSK3A; 606784) and beta, show a high degree of amino acid homology (Stambolic and Woodgett, 1994). GSK3B is involved in energy metabolism, neuronal cell development, and body pattern formation.

Wikipedia summary for GSK3B:

Glycogen synthase kinase 3 beta, also known as GSK3B, is an enzyme that in humans is encoded by the GSK3B gene.

Human GSK3B Protein General Information

 

• Protein names: Glycogen synthase kinase-3 beta, Short name=GSK3B
• Sequence length: 420 AA.
• Sequence similarities: Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family. GSK-3 subfamily. Contains 1 protein kinase domain.
• Post-translational modification: 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.
• 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.
• Catalytic activity: ATP + [tau protein] = ADP + [tau protein]
  phosphate.ATP + a protein = ADP + a phosphoprotein.
• Enzyme regulation: GSK3B is activated by phosphorylation at Tyr-216. In response to insulin, GSK3B is 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. GSK3B is inhibited by lithium.
• Miscellaneous: Higher expression and activity of GSK3B are found in the skeletal muscle (vastus lateralis) of patients with type 2 diabetes. Several potent GSK3 (GSK3A and GSK3B) inhibitors have been identified and characterized in preclinical models for treatments of type 2 diabetes.

General information above from UniProt

Function for GSK3B Protein

UniProtKB:

Glycogen synthase kinase-3 (GSK-3) is a proline-directed serine-threonine kinase that was initially identified as a phosphorylating and an inactivating agent of 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.

Genatlas:

• GSK3B is involved in energy metabolism, neuronal cell development, and body pattern formation
• glycogen synthase kinase, dual specificity protein-kinase
• GSK3B regulats glycogen synthesis in skeletal muscle through Tyr (activating) or Ser/Thr (inactivating) phosphorylation
• key downstream target of PI3-kinase/AKT survival signaling pathway and GSK3B is involved in the regulation of apoptosis
• GSK3B phosphorylats DPYSL2 and regulating neuronal polarity
• GSK3B may function as a repressor to suppress androgen receptor-mediated transactivation and cell growth
• GSK3B regulats microtubule growth and stability, phosphorylating many microtubule associated proteins such as tau, MAP1b and CRMP-2 or APC
• GSK3B plays an essential role for axon outgrowth
• GSK3B is involved in the apoptotic stimulus, and thus in the process of neuronal cell death (Pubmed 17612578)
• GSK3B is involved in the regulation of the cell cycle in cerebellar granule cells (Pubmed 17612578)
• GSK3B has a unique role in regulating death receptor-induced apoptosis, GSK3B is the only enzyme known to act proximal to the four major death receptors to inhibit the initiation of apoptotic signaling by blocking CASP8 activation (Pubmed 18846110)
• a downstream effector of PI3K that phosphorylates proteins involved in regulating microtubule dynamics and microtubule-based transport
• GSK3B plays a role in control neurogenesis, neuronal polarization and axon growth and guidance during brain development (Pubmed 20648061)
• GSK3B negatively regulates the expression of the adherens junction protein CDH1, thereby influencing barrier function and inhibiting epithelial–mesenchymal transition (EMT)(Pubmed 20685350)
• with THRAP3, GSK3B plays a role in the complex network that regulates PTPRC alternative splicing (Pubmed 20932480)

Homology for human GSK3B

• homolog to Drosophila Shaggy-Zeste-White 3
• ortholog to Gsk3b, Mus musculus
• ortholog to rGsk3b, Rattus norvegicus
• ortholog to gsk3b, danio rerio
• ortholog to GSK3B, Pan troglodytes
• homolog to GSK3A

Drugs for GSK3B

Target	Drug Name	Drug Status	Disease
GSK3B	Enzastaurin	Phase I	Brain and Central Nervous System Tumors
GSK3B	Enzastaurin	Phase II	Glioblastoma Multiforme
GSK3B	Enzastaurin	Phase III	Non Hodgkin Lymphoma

Drugs for GSK3B from TTD (Therapeutic Targets Database)