Regulation of mTOR by phosphatidic acid.
FRB
Rheb
mTOR
phosphatidic acid
phospholipase D
structure
Journal
Trends in endocrinology and metabolism: TEM
ISSN: 1879-3061
Titre abrégé: Trends Endocrinol Metab
Pays: United States
ID NLM: 9001516
Informations de publication
Date de publication:
03 2023
03 2023
Historique:
received:
19
11
2022
accepted:
03
01
2023
pmc-release:
01
03
2024
pubmed:
3
2
2023
medline:
18
2
2023
entrez:
2
2
2023
Statut:
ppublish
Résumé
mTORC1, the mammalian target of rapamycin complex 1, is a key regulator of cellular physiology. The lipid metabolite phosphatidic acid (PA) binds to and activates mTORC1 in response to nutrients and growth factors. We review structural findings and propose a model for PA activation of mTORC1. PA binds to a highly conserved sequence in the α4 helix of the FK506 binding protein 12 (FKBP12)/rapamycin-binding (FRB) domain of mTOR. It is proposed that PA binding to two adjacent positively charged amino acids breaks and shortens the C-terminal region of helix α4. This has profound consequences for both substrate binding and the catalytic activity of mTORC1.
Identifiants
pubmed: 36732094
pii: S1043-2760(23)00015-2
doi: 10.1016/j.tem.2023.01.004
pmc: PMC9957947
mid: NIHMS1870525
pii:
doi:
Substances chimiques
Phosphatidic Acids
0
TOR Serine-Threonine Kinases
EC 2.7.11.1
Mechanistic Target of Rapamycin Complex 1
EC 2.7.11.1
Amino Acids
0
MTOR protein, human
EC 2.7.1.1
Types de publication
Journal Article
Review
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
170-180Subventions
Organisme : NCI NIH HHS
ID : R01 CA046677
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA179542
Pays : United States
Informations de copyright
Copyright © 2023 Elsevier Ltd. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of interests The authors declare no conflicts of interest.
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