Glycogen synthase kinase (GSK)-3 and the double-strand RNA-dependent kinase, PKR: When two kinases for the common good turn bad.
Alternative splicing
Inflammation
Innate immunity
Leukemia
Neurodegenerative disease
Osteosarcoma
Journal
Biochimica et biophysica acta. Molecular cell research
ISSN: 1879-2596
Titre abrégé: Biochim Biophys Acta Mol Cell Res
Pays: Netherlands
ID NLM: 101731731
Informations de publication
Date de publication:
10 2020
10 2020
Historique:
received:
31
03
2020
revised:
29
05
2020
accepted:
31
05
2020
pubmed:
9
6
2020
medline:
15
12
2020
entrez:
9
6
2020
Statut:
ppublish
Résumé
Glycogen synthase kinase (GSK)-3α/β and the double-stranded RNA-dependent kinase PKR are two sentinel kinases that carry-out multiple similar yet distinct functions in both the cytosol and the nucleus. While these kinases belong to separate signal transduction cascades, they demonstrate an uncanny propensity to regulate many of the same proteins either through direct phosphorylation or by altering transcription/translation, including: c-MYC, NF-κB, p53 and TAU, as well as each another. A significant number of studies centered on the GSK3 kinases have led to the identification of the GSK3 interactome and a number of substrates, which link GSK3 activity to metabolic control, translation, RNA splicing, ribosome biogenesis, cellular division, DNA repair and stress/inflammatory signaling. Interestingly, many of these same pathways and processes are controlled by PKR, but unlike the GSK3 kinases, a clear picture of proteins interacting with PKR and a complete listing of its substrates is still missing. In this review, we take a detailed look at what is known about the PKR and GSK3 kinases, how these kinases interact to influence common cellular processes (innate immunity, alternative splicing, translation, glucose metabolism) and how aberrant activation of these kinases leads to diseases such as Alzheimer's disease (AD), diabetes mellitus (DM) and cancer.
Identifiants
pubmed: 32512016
pii: S0167-4889(20)30127-0
doi: 10.1016/j.bbamcr.2020.118769
pmc: PMC7273171
pii:
doi:
Substances chimiques
eIF-2 Kinase
EC 2.7.11.1
Glycogen Synthase Kinase 3
EC 2.7.11.26
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
118769Informations de copyright
Copyright © 2020 Elsevier B.V. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
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