S6K1-mediated phosphorylation of PDK1 impairs AKT kinase activity and oncogenic functions.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
22 03 2022
22 03 2022
Historique:
received:
09
05
2021
accepted:
16
02
2022
entrez:
23
3
2022
pubmed:
24
3
2022
medline:
13
4
2022
Statut:
epublish
Résumé
Functioning as a master kinase, 3-phosphoinositide-dependent protein kinase 1 (PDK1) plays a fundamental role in phosphorylating and activating protein kinases A, B and C (AGC) family kinases, including AKT. However, upstream regulation of PDK1 remains largely elusive. Here we report that ribosomal protein S6 kinase beta 1 (S6K1), a member of AGC kinases and downstream target of mechanistic target of rapamycin complex 1 (mTORC1), directly phosphorylates PDK1 at its pleckstrin homology (PH) domain, and impairs PDK1 interaction with and activation of AKT. Mechanistically, S6K1-mediated phosphorylation of PDK1 augments its interaction with 14-3-3 adaptor protein and homo-dimerization, subsequently dissociating PDK1 from phosphatidylinositol 3,4,5 triphosphate (PIP
Identifiants
pubmed: 35318320
doi: 10.1038/s41467-022-28910-8
pii: 10.1038/s41467-022-28910-8
pmc: PMC8941131
doi:
Substances chimiques
3-Phosphoinositide-Dependent Protein Kinases
EC 2.7.11.1
Protein Serine-Threonine Kinases
EC 2.7.11.1
Proto-Oncogene Proteins c-akt
EC 2.7.11.1
Ribosomal Protein S6 Kinases, 70-kDa
EC 2.7.11.1
ribosomal protein S6 kinase, 70kD, polypeptide 2
EC 2.7.11.1
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1548Informations de copyright
© 2022. The Author(s).
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