Ligand-independent interaction of the type I interferon receptor complex is necessary to observe its biological activity.

ABSTRACT: Ectopic coexpression of the two chains of the Type I and Type III interferon (IFN) receptor complexes (IFN-?R1 and IFN-?R2c, or IFN-?R1 and IL-10R2) yielded sensitivity to IFN-alpha or IFN-lambda in only some cells. We found that IFN-?R1 and IFN-?R2c exhibit FRET only when expressed at equivalent and low levels. Expanded clonal cell lines expressing both IFN-?R1 and IFN-?R2c were sensitive to IFN-alpha only when IFN-?R1 and IFN-?R2c exhibited FRET in the absence of human IFN-alpha. Coexpression of RACK-1 or Jak1 enhanced the affinity of the interaction between IFN-?R1 and IFN-?R2c. Both IFN-?R1 and IFN-?R2c exhibited FRET with Jak1 and Tyk2. Together with data showing that disruption of the preassociation between the IFN-gamma receptor chains inhibited its biological activity, we propose that biologically active IFN receptors require ligand-independent juxtaposition of IFN receptor chains assisted by their associated cytosolic proteins.

SUBMITTER: Krause CD 

PROVIDER: S-EPMC3770802 | biostudies-other | 2013 Oct

REPOSITORIES: biostudies-other