Role of the Akt pathway in mRNA translation of interferon-stimulated genes

Surinder Kaur, Antonella Sassano, Blazej Dolniak, Sonali Joshi, Beata Majchrzak-Kita, Darren P. Baker, Nissim Hay, Eleanor N. Fish, Leonidas C. Platanias

Research output: Contribution to journalArticlepeer-review

149 Scopus citations

Abstract

Multiple signaling pathways are engaged by the type I and II IFN receptors, but their specific roles and possible coordination in the generation of IFN-mediated biological responses remain unknown. We provide evidence that activation of Akt kinases is required for IFN-inducible engagement of the mTOR/p70 S6 kinase pathway. Our data establish that Akt activity is essential for up-regulation of key IFN-α- and IFN-γ-inducible proteins, which have important functional consequences in the induction of IFN responses. Such effects of the Akt pathway are unrelated to regulatory activities on IFN-dependent STAT phosphorylation/activation or transcriptional regulation. By contrast, they reflect regulatory activities on mRNA translation via direct control of the mTOR pathway. In studies using Akt1 and Akt2 double knockout cells, we found that the absence of Akt kinases results in dramatic reduction in IFN-induced antiviral responses, establishing a critical role of the Akt pathway in IFN signaling. Thus, activation of the Akt pathway by the IFN receptors complements the function of IFN-activated JAK-STAT pathways, by allowing mRNA translation of IFN-stimulated genes and, ultimately, the induction of the biological effects of IFNs.

Original languageEnglish (US)
Pages (from-to)4808-4813
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume105
Issue number12
DOIs
StatePublished - Mar 25 2008

ASJC Scopus subject areas

  • General

Fingerprint Dive into the research topics of 'Role of the Akt pathway in mRNA translation of interferon-stimulated genes'. Together they form a unique fingerprint.

Cite this