The Receptor of the Type I Interferon Family

Uzé, Gilles; Schreiber, Gideon; Piehler, Jacob; Pellegrini, Sandra

doi:10.1007/978-3-540-71329-6_5

Cited by 155 publications

(74 citation statements)

References 97 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These IFNs bind to a heteromeric receptor composed of two subunits, IFNaR1 and IFNaR2 [3,4], which utilize the JAK tyrosine kinases, Jak1 and Tyk2, and STAT transcription factors, including Stat1 and Stat2, to modulate gene transcription [5]. IFN binding triggers receptor dimerization and activation of the receptor associated JAKs, which in turn phosphorylate a key tyrosine residue on IFNaR1, creating a docking site for Stat2 [6].…”

Section: Introductionmentioning

confidence: 99%

Nuclear transit of the intracellular domain of the interferon receptor subunit IFNaR2 requires Stat2 and Irf9

Fiky

Pioli

Azam

et al. 2008

Cellular Signalling

View full text Add to dashboard Cite

Regulated intramembrane proteolysis (RIP) is the primary signaling mechanism for some receptors, such as Notch and the amyloid precursor protein. In addition, some receptor type tyrosine kinases, such as HER4, are able to signal via both kinase activation and regulated receptor proteolysis. Previously, we showed that the IFNaR2 subunit of the type I interferon receptor can be cleaved in a two step process that resembles RIP and that the IFNaR2 intracellular domain (IFNaR2-ICD) can mediate gene transcription in a Stat2 dependent manner. Here, we demonstrate that IFNaR2-ICD, Stat2 and Irf9 form a ternary complex. Furthermore, Stat2 and Irf9 are required for the nuclear transit of a GFP-linked IFNaR2-ICD construct (GFP-ICD). Additional experiments monitoring the nuclear localization of GFP-ICD demonstrate that Stat2 serves an adaptor role, mediating the interaction between the IFNaR2-ICD and Irf9, while the bipartite nuclear localization signal within Irf9 is the primary determinant driving nuclear transit of the ICD containing complex. Overall, the data suggest that liberation of the IFNaR2-ICD by regulated proteolysis could trigger a novel mechanism for moving the transcription factor Stat2 to the nucleus.

show abstract

Section: Introductionmentioning

confidence: 99%

Nuclear transit of the intracellular domain of the interferon receptor subunit IFNaR2 requires Stat2 and Irf9

Fiky

Pioli

Azam

et al. 2008

Cellular Signalling

View full text Add to dashboard Cite

show abstract

“…The efficacy of induction of antiviral responses appears different between subclasses and even between subtypes belonging to the same subclass. For example, human IFN-␣ subtypes vary in their ability to activate human natural killer cells, and IFN-␤ shows more potency than IFN-␣2 in inhibition of monocyte proliferation (8,41,43). Therefore, to elucidate the antiviral potency of a type I IFN family, it is essential to systematically analyze their antiviral activity among members of the same and different subclasses.…”

mentioning

confidence: 99%

Differential expression and activity of the porcine type I interferon family

Sang¹,

Rowland

Hesse

et al. 2010

Physiological Genomics

193

View full text Add to dashboard Cite

Type I interferons (IFNs) are central to innate and adaptive immunity, and many have unique developmental and physiological functions. However, in most species, only two subtypes, IFN-α and IFN-β, have been well studied. Because of the increasing importance of zoonotic viral diseases and the use of pigs to address human research questions, it is important to know the complete repertoire and activity of porcine type I IFNs. Here we show that porcine type I IFNs comprise at least 39 functional genes distributed along draft genomic sequences of chromosomes 1 and 10. These functional IFN genes are classified into 17 IFN-α subtypes, 11 IFN-δ subtypes, 7 IFN-ω subtypes, and single-subtype subclasses of IFN-αω, IFN-β, IFN-ε, and IFN-κ. We found that porcine type I IFNs have diverse expression profiles and antiviral activities against porcine reproductive and respiratory syndrome virus (PRRSV) and vesicular stomatitis virus (VSV), with activity ranging from 0 to >105 U·ng−1·ml−1. Whereas most IFN-α subtypes retained the greatest antiviral activity against both PRRSV and VSV in porcine and MARC-145 cells, some IFN-δ and IFN-ω subtypes, IFN-β, and IFN-αω differed in their antiviral activity based on target cells and viruses. Several IFNs, including IFN-α7/11, IFN-δ2/7, and IFN-ω4, exhibited minimal or no antiviral activity in the tested target cell-virus systems. Thus comparative studies showed that antiviral activity of porcine type I IFNs is virus- and cell-dependent, and IFN-αs are positively correlated with induction of MxA, an IFN-stimulated gene. Collectively, these data provide fundamental genomic information for porcine type I IFNs, information that is necessary for understanding porcine physiological and antiviral responses.

show abstract

“…[35][36][37] Once secreted from infected cells, these IFNs initiate the antiviral responses by inducing the expression of the IFN-stimulated genes (ISGs) involved in innate and adaptive immunity. 38,39 The first clue of a possible role of Optn in an antiviral immune response came from its ability to interact with TANK-binding kinase 1 (TBK1), a protein kinase membrane. 34 The detailed examination of the fusion defects reveals that knockdown of Optineurin or Myosin VI results in an increase in the proportion of incomplete fusion events and in the number of docked vesicles present at the plasma membrane (Fig.…”

mentioning

confidence: 99%