Glycogen Synthase Kinase 3 Beta

From Anvita Health Wiki

Contents 1 Function 2 Structure 3 Alternative-splicing 4 Expression 5 Pathology 6 More General Terms 7 Additional Terms 8 Internet Database 9 References

Function

• proline-directed serine-threonine kinase that phosphorylates & inactivates glycogen synthase
• involved in energy metabolism, neuronal cell development, & body pattern formation
• role in hippocampal consolidation & reconsolidation of memories
• role in the Wnt signaling pathway
• implicated in hormonal control of several regulatory proteins including glycogen synthase, MYB & the transcription factor JUN
• phosphorylates JUN proximal to its DNA-binding domain, thus diminishing JUN's affinity for DNA
• phosphorylates MUC1 in breast cancer cells, & decreases interaction of MUC1 with CTNNB1/ beta-catenin
• inhibited when phosphorylated by AKT1
• phosphorylated by AKT1 & ILK1
• Akt phosphorylates GSK3B on Ser-9 & inactivates GSK3B
• protein kinase C delta also phosphorylates & inactivates GSK3B [4]
• GSK3B is inactivated by insulin
• phosphorylation of Ser 9 inactivates GSK3B, whereas phosphorylation of Tyr 216 is required for activity
• GSK3B phosphorylates beta-catenin resulting in ubiquitin mediated proteolysis
• GSK3B associates with & activates MEKK1, stimulating the JNK/ SAPK pathway
• interacts with MUC1, NIN & CABYR

Structure

• monomer ( putative).
• belongs to the protein kinase superfamily, CMGC Ser/Thr protein kinase family, GSK-3 subfamily
• contains 1 protein kinase domain Asp 181 lies within the active site

Alternative-splicing

• named isoforms=2

Expression

• expressed in testis, thymus, prostate & ovary > lung, brain & kidney

Pathology

• inadvertantly, GSK3B may also hyperphosphorylate microtubule- associated protein tau leading to formation of paired helical filaments [2]

More General Terms

• glycogen synthase kinase 3 (GSK3)

Additional Terms

• glycogen synthase
• microtubule-associated protein tau (neurofibrillary tangle protein, paired helical filament-tau, PHF-tau, MAPT, MTBT1)
• paired helical filament (PHF)

Internet Database

UniProt: [1]
Kegg: [2]
OMIM: 605004
Prosite: [3]
Prosite: [4]
Prosite: [5]
Entrez gene: 2932

References

1. OMIM [6]
2. Maccioni et al The molecular bases of Alzheimer's disease and other neurodegenerative disorders. Archives of Medical Research 32:367, 2001 PMID: [7]
3. Kim et al, Glycogen synthase kinase 3 beta is a natural activator of mitogen-activated protein kinase/extracellular signal-regulated kinase kinase kinase 1 (MEKK1) J Biol Chem 278(16):13995-14001, 2003 PMID: [8]
4. Tsujio et al, Inactivation of glycogen synthase kinase-3 by protein kinase C delta: implications for regulation of tau phosphorylation. FEBS Lett 469:111-117, 2000 PMID: [9]
5. UniProt [10]

glycogen synthase kinase 3-beta (GSK3B)