Regulatory effects of mTORC2 complexes in type I IFN signaling and in the generation of IFN responses

Surinder Kaur, Antonella Sassano, Beata Majchrzak-Kita, Darren P. Baker, Bing Su, Eleanor N. Fish, Leonidas C. Platanias*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

38 Scopus citations

Abstract

IFNs transduce signals by binding to cell surface receptors and activating cellular pathways and regulatory networks that control transcription of IFN-stimulated genes (ISGs) and mRNA translation, leading to generation of protein products that mediate biological responses. Previous studies have shown that type I IFN receptor-engaged pathways downstream of AKT and mammalian target of rapamycin complex (mTORC) 1 play important roles in mRNA translation of ISGs and the generation of IFN responses, but the roles of mTORC2 complexes in IFN signaling are unknown. We provide evidence that mTORC2 complexes control IFN-induced phosphorylation of AKT on serine 473 and their function is ultimately required for IFN-dependent gene transcription via interferon-stimulated response elements. We also demonstrate that such complexes exhibit regulatory effects on other IFN-dependent mammalian target of rapamycin-mediated signaling events, likely via engagement of the AKT/mTORC1 axis, including IFN-induced phosphorylation of S6 kinase and its effector rpS6, as well as phosphorylation of the translational repressor 4E-binding protein 1. We also show that induction of ISG protein expression and the generation of antiviral responses are defective in Rictor and mLST8-KO cells. Together, our data provide evidence for unique functions of mTORC2 complexes in the induction of type I IFN responses and suggest a critical role for mTORC2-mediated signals in IFN signaling.

Original languageEnglish (US)
Pages (from-to)7723-7728
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume109
Issue number20
DOIs
StatePublished - May 15 2012

ASJC Scopus subject areas

  • General

Fingerprint Dive into the research topics of 'Regulatory effects of mTORC2 complexes in type I IFN signaling and in the generation of IFN responses'. Together they form a unique fingerprint.

Cite this