Dual regulatory roles of phosphatidylinositol 3-kinase in IFN signaling

Surinder Kaur, Antonella Sassano, Ajith M. Joseph, Beata Majchrzak-Kita, Elizabeth A. Eklund, Amit K. Verma, Saskia M. Brachmann, Eleanor N. Fish, Leonidas C. Platanias

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Abstract

PI3K is activated by the type I and II IFN receptors, but its precise role in the generation of IFN responses is not well understood. In the present study we used embryonic fibroblasts from mice with targeted disruption of the genes encoding for both the p85α and p85β regulatory subunits of PI3′-kinase (p85α-/-β-/-) to precisely define the role of PI3K in the control of IFN-induced biological responses. Our data demonstrate that PI3K plays dual regulatory roles in the induction of IFN responses by controlling both IFN-α- and IFN-γ-dependent transcriptional regulation of IFN-sensitive genes and simultaneously regulating the subsequent initiation of mRNA translation for such genes. These processes include the Isg15, Cxcl10, and/or Irf7 genes, whose functions are important in the generation of the biological effects of IFNs. Consistent with this, the induction of IFN antiviral responses is defective in double p85α/p85β knockout cells. Thus, integration of signals via PI3K is a critical event during engagement of the IFN receptors that complements both the transcriptional activity of Jak-STAT pathways and controls initiation of mRNA translation.

Original languageEnglish (US)
Pages (from-to)7316-7323
Number of pages8
JournalJournal of Immunology
Volume181
Issue number10
StatePublished - Nov 15 2008

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Phosphatidylinositol 3-Kinase
Phosphatidylinositol 3-Kinases
Protein Biosynthesis
Genes
Complement Receptors
Cohort Effect
Antiviral Agents
Fibroblasts

ASJC Scopus subject areas

  • Immunology
  • Medicine(all)

Cite this

Kaur, S., Sassano, A., Joseph, A. M., Majchrzak-Kita, B., Eklund, E. A., Verma, A. K., ... Platanias, L. C. (2008). Dual regulatory roles of phosphatidylinositol 3-kinase in IFN signaling. Journal of Immunology, 181(10), 7316-7323.

Dual regulatory roles of phosphatidylinositol 3-kinase in IFN signaling. / Kaur, Surinder; Sassano, Antonella; Joseph, Ajith M.; Majchrzak-Kita, Beata; Eklund, Elizabeth A.; Verma, Amit K.; Brachmann, Saskia M.; Fish, Eleanor N.; Platanias, Leonidas C.

In: Journal of Immunology, Vol. 181, No. 10, 15.11.2008, p. 7316-7323.

Research output: Contribution to journalArticle

Kaur, S, Sassano, A, Joseph, AM, Majchrzak-Kita, B, Eklund, EA, Verma, AK, Brachmann, SM, Fish, EN & Platanias, LC 2008, 'Dual regulatory roles of phosphatidylinositol 3-kinase in IFN signaling', Journal of Immunology, vol. 181, no. 10, pp. 7316-7323.
Kaur S, Sassano A, Joseph AM, Majchrzak-Kita B, Eklund EA, Verma AK et al. Dual regulatory roles of phosphatidylinositol 3-kinase in IFN signaling. Journal of Immunology. 2008 Nov 15;181(10):7316-7323.
Kaur, Surinder ; Sassano, Antonella ; Joseph, Ajith M. ; Majchrzak-Kita, Beata ; Eklund, Elizabeth A. ; Verma, Amit K. ; Brachmann, Saskia M. ; Fish, Eleanor N. ; Platanias, Leonidas C. / Dual regulatory roles of phosphatidylinositol 3-kinase in IFN signaling. In: Journal of Immunology. 2008 ; Vol. 181, No. 10. pp. 7316-7323.
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