glycogen synthase kinase 3-beta (GSK3B)
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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
Pathology
- inadvertantly, GSK3B may also hyperphosphorylate microtubule-associated protein tau leading to formation of paired helicalfilaments[2]
More general terms
Additional terms
- glycogen synthase
- microtubule-associated protein tau (neurofibrillary tangle protein, paired helical filament-tau, PHF-tau, MAPT, MTBT1)
- paired helical filament (PHF)
References
- ↑ OMIM https://mirror.omim.org/entry/605004
- ↑ 2.0 2.1 Maccioni et al The molecular bases of Alzheimer's disease and other neurodegenerative disorders. Archives of Medical Research 32:367, 2001 PMID: https://www.ncbi.nlm.nih.gov/pubmed/11578751
- ↑ 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: https://www.ncbi.nlm.nih.gov/pubmed/12584189
- ↑ 4.0 4.1 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: https://www.ncbi.nlm.nih.gov/pubmed/10708767
- ↑ UniProt http://www.uniprot.org/uniprot/P49841.html