Glycogen synthase kinase-3 beta, (GSK-3 beta), is an enzyme that in humans is encoded by the GSK3B gene. In mice, the enzyme is encoded by the Gsk3b gene. Abnormal regulation and expression of GSK-3 beta is associated with an increased susceptibility towards bipolar disorder.

Function

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.

Disease relevance

Homozygous disruption of the Gsk3b locus in mice results in embryonic lethality during mid-gestation. This lethality phenotype could be rescued by inhibition of tumor necrosis factor.

Two SNPs at this gene, rs334558 (-50T/C) and rs3755557 (-1727A/T), are associated with efficacy of lithium treatment in bipolar disorder.

Signaling pathways

Pharmacological inhibition of ERK1/2 restores GSK-3 beta activity and protein synthesis levels in a model of tuberous sclerosis.

Interactions

GSK3B has been shown to interact with:

Overview of signal transduction pathways involved in apoptosis.

See also

  • GSK-3 – Class of enzymes

Further reading

  • Turenne GA, Price BD (2001). . BMC Cell Biology. 2 12. doi:. PMC . PMID .
  • Plyte SE, Hughes K, Nikolakaki E, Pulverer BJ, Woodgett JR (December 1992). "Glycogen synthase kinase-3: functions in oncogenesis and development". Biochimica et Biophysica Acta (BBA) - Reviews on Cancer. 1114 (2–3): 147–62. doi:. PMID .
  • Morishima-Kawashima M, Hasegawa M, Takio K, Suzuki M, Yoshida H, Watanabe A, et al. (1995). "Hyperphosphorylation of tau in PHF". Neurobiology of Aging. 16 (3): 365–71, discussion 371–80. doi:. PMID . S2CID .
  • Jope RS, Bijur GN (2002). . Molecular Psychiatry. 7 (Suppl 1): S35-45. doi:. PMID .
  • Bhat RV, Budd SL (2003). "GSK3beta signalling: casting a wide net in Alzheimer's disease". Neuro-Signals. 11 (5): 251–61. doi:. PMID . S2CID .
  • Wang W, Li M, Wang Y, Li Q, Deng G, Wan J, et al. (December 2016). . Molecular Neurobiology. 53 (10): 7028–7036. doi:. PMC . PMID .
  • Nadri C, Kozlovsky N, Agam G (September 2003). "[Schizophrenia, neurodevelopment and glycogen synthase kinase-3]". Harefuah. 142 (8–9): 636–42, 644. PMID .
  • Mulholland DJ, Dedhar S, Wu H, Nelson CC (January 2006). . Oncogene. 25 (3): 329–37. doi:. PMID .

External links

  • provides an overview of all the structure information available in the PDB for Human Glycogen synthase kinase-3 beta (GSK3B)