Loss of PI3k activity of inositol polyphosphate multikinase impairs PDK1-mediated AKT activation, cell migration, and intestinal homeostasis.
Cell biology
Gastroenterology
Molecular biology
Journal
iScience
ISSN: 2589-0042
Titre abrégé: iScience
Pays: United States
ID NLM: 101724038
Informations de publication
Date de publication:
19 May 2023
19 May 2023
Historique:
received:
05
06
2022
revised:
22
02
2023
accepted:
03
04
2023
medline:
22
5
2023
pubmed:
22
5
2023
entrez:
22
5
2023
Statut:
epublish
Résumé
Protein kinase B (AKT) is essential for cell survival, proliferation, and migration and has been associated with several diseases. Here, we demonstrate that inositol polyphosphate multikinase (IPMK's) lipid kinase property drives AKT activation via increasing membrane localization and activation of PDK1 (3-Phosphoinositide-dependent kinase 1), largely independent of class I PI3k (cPI3K). Deletion of IPMK impairs cell migration, which is partially associated with the abolition of PDK1-mediated ROCK1 disinhibition and subsequent myosin light chain (MLC) phosphorylation. IPMK is highly expressed in intestinal epithelial cells (IEC). Deleting IPMK in IEC reduced AKT phosphorylation and diminished the number of Paneth cells. Ablation of IPMK impaired IEC regeneration both basally and after chemotherapy-induced damage, suggesting a broad role for IPMK in activating AKT and intestinal tissue regeneration. In conclusion, the PI3k activity of IPMK is necessary for PDK1-mediated AKT activation and intestinal homeostasis.
Identifiants
pubmed: 37216099
doi: 10.1016/j.isci.2023.106623
pii: S2589-0042(23)00700-9
pmc: PMC10197106
doi:
Types de publication
Journal Article
Langues
eng
Pagination
106623Subventions
Organisme : NCI NIH HHS
ID : P30 CA008748
Pays : United States
Informations de copyright
© 2023 The Author(s).
Déclaration de conflit d'intérêts
The authors declare no competing interests.
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