Methionine controls insulin/mammalian target of rapamycin complex 1 activity by modulating tuberous sclerosis complex 2 stability.
HEK293 Cells
HeLa Cells
Homeodomain Proteins
/ metabolism
Humans
Insulin
/ metabolism
Intracellular Signaling Peptides and Proteins
/ metabolism
Mechanistic Target of Rapamycin Complex 1
/ metabolism
Methionine
/ metabolism
Methylation
Phosphorylation
Protein Stability
Proteolysis
Proto-Oncogene Proteins c-akt
/ metabolism
Signal Transduction
Tuberous Sclerosis Complex 2 Protein
/ chemistry
AKT
Amino acid
Mammalian target of rapamycin complex 1
Methionine
S-adenosylmethionine
Tuberous sclerosis complex 2
Journal
Biochemical and biophysical research communications
ISSN: 1090-2104
Titre abrégé: Biochem Biophys Res Commun
Pays: United States
ID NLM: 0372516
Informations de publication
Date de publication:
19 02 2021
19 02 2021
Historique:
received:
07
01
2021
accepted:
11
01
2021
pubmed:
23
1
2021
medline:
14
8
2021
entrez:
22
1
2021
Statut:
ppublish
Résumé
Tuberous sclerosis complex 2 (TSC2) is a tumor-suppressor protein that is partially regulated by insulin, energy, oxygen, and growth factors. Mutations in the TSC2 gene and loss of TSC2 promote cell growth by the mammalian target of rapamycin complex 1 (mTORC1) activation. Furthermore, S-adenosylmethionine (SAM) sensor upstream of mTORC1 indirectly inhibits mTORC1 activity via the methionine metabolite SAM. Here, we investigated the effects of methionine on insulin/TSC2/mTORC1 activity. Our results showed that methionine affected TSC2 stability and abolished TSC2 localization to the lysosome. Moreover, activation of insulin signaling contributed to TSC2 degradation in a methionine deprivation-dependent manner. Thus, methionine and insulin crosstalk occurred via TSC2.
Identifiants
pubmed: 33482580
pii: S0006-291X(21)00068-1
doi: 10.1016/j.bbrc.2021.01.033
pii:
doi:
Substances chimiques
BMT2 protein, human
0
Homeodomain Proteins
0
Insulin
0
Intracellular Signaling Peptides and Proteins
0
TSC2 protein, human
0
Tuberous Sclerosis Complex 2 Protein
0
RAG-1 protein
128559-51-3
Methionine
AE28F7PNPL
Mechanistic Target of Rapamycin Complex 1
EC 2.7.11.1
Proto-Oncogene Proteins c-akt
EC 2.7.11.1
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
84-89Informations de copyright
Copyright © 2021 Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of competing interest The authors declare no competing financial interests.