| First Author | Gan X | Year | 2012 |
| Journal | Nat Cell Biol | Volume | 14 |
| Issue | 7 | Pages | 686-96 |
| PubMed ID | 22609986 | Mgi Jnum | J:190487 |
| Mgi Id | MGI:5448916 | Doi | 10.1038/ncb2507 |
| Citation | Gan X, et al. (2012) PRR5L degradation promotes mTORC2-mediated PKC-delta phosphorylation and cell migration downstream of Galpha12. Nat Cell Biol 14(7):686-96 |
| abstractText | 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-delta hydrophobic motif phosphorylation. The late phase is mediated by Galpha(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-delta, but not AKT, results in PKC-delta hydrophobic motif phosphorylation and activation. This Galpha(12)-mediated signalling pathway for mTORC2 regulation is critically important for fibroblast migration and pulmonary fibrosis development. |
