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glycogen synthase kinase 3-beta (GSK3B)

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 helicalfilaments [2]

Related

glycogen synthase insulin for injection (Novolin, Humulin, Lente, Semilente, Ultralente, Iletin, NPH (isophane), PZI, INS) microtubule-associated protein tau (neurofibrillary tangle protein, paired helical filament-tau, PHF-tau, MAPT, MTBT1, m-tau, mtau) paired helical filament (PHF)

General

glycogen synthase kinase 3 (GSK3)

Properties

SIZE: entity length = 420 aa MW = 47 kD STATE: active state MOTIF: Thr phosphorylation site {T7} Ser phosphorylation site {S9} kinase domain SITE: 56-340 MOTIF: ATP-binding site NAME: ATP-binding site SITE: 62-70 ATP-binding site NAME: ATP-binding site SITE: 85-85 aspartate residue {D181} Ser phosphorylation site {S215} Tyr-phosphate {Y216} Ser phosphorylation site {S219} Ser phosphorylation site {S389} Thr phosphorylation site {T390} Thr phosphorylation site {T395}

References

  1. OMIM :accession 605004
  2. Maccioni et al The molecular bases of Alzheimer's disease and other neurodegenerative disorders. Archives of Medical Research 32:367, 2001 PMID: 11578751
  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: 12584189
  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: 10708767
  5. UniProt :accession P49841

Databases & Figures

OMIM 605004 UniProt P49841 Pfam PF00069 Entrez Gene 2932 Kegg hsa:2932 ENZYME 2.7.11.26 RTK -> PI-3-kinase -> Akt -> ...