PRR5L degradation promotes mTORC2-mediated PKC-δ phosphorylation and cell migration downstream of Gα12.
Nat Cell Biol
; 14(7): 686-96, 2012 May 20.
Article
de En
| MEDLINE
| ID: mdl-22609986
ABSTRACT
Mammalian target of rapamycin complex 2 (mTORC2) phosphorylates AGC protein kinases including protein kinase C (PKC) and regulates cellular functions such as cell migration. However, its regulation remains poorly understood. Here we show that lysophosphatidic acid (LPA) induces two phases of PKC-δ hydrophobic motif phosphorylation. The late phase is mediated by Gα(12), which specifically activates ARAF, leading to upregulation of the RFFL E3 ubiquitin ligase and subsequent ubiquitylation and degradation of the PRR5L subunit of mTORC2. Destabilization of PRR5L, a suppressor of mTORC2-mediated hydrophobic motif phosphorylation of PKC-δ, but not AKT, results in PKC-δ hydrophobic motif phosphorylation and activation. This Gα(12)-mediated signalling pathway for mTORC2 regulation is critically important for fibroblast migration and pulmonary fibrosis development.
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Fibrose pulmonaire
/
Protéines
/
Transactivateurs
/
Sous-unités alpha G12-G13 des protéines G
/
Complexes multiprotéiques
/
Protein kinase C-delta
/
Sérine-thréonine kinases TOR
/
Fibroblastes
/
Poumon
Type d'étude:
Prognostic_studies
Langue:
En
Journal:
Nat Cell Biol
Année:
2012
Type de document:
Article
Pays d'affiliation:
États-Unis d'Amérique