HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Costa-Pereira, A. P. Articles by Kerr, I. M. Search for Related Content PubMed PubMed Citation Articles by Costa-Pereira, A. P. Articles by Kerr, I. M.

Signaling through a Mutant IFN- Receptor

Ana P. Costa-Pereira^1,2,*, Heike M. Hermanns^2,, Hayaatun Is’harc^2,*, Timothy M. Williams^2,*, Diane Watling^2,*, Velmurugesan Arulampalam, Sally J. Newman^*, Peter C. Heinrich and Ian M. Kerr^*

^* Cancer Research U.K., London Research Institute, Lincoln’s Inn Fields Laboratories, London, United Kingdom; Institut fuer Biochemie, Uniklinik Rheinisch-Westfaelische Technische Hochschule Aachen, Aachen, Germany; and Microbiology and Tumor Biology Centre, Karolinska Institute, Stockholm, Sweden

Activation of STAT1 and the IFN- response are thought to be mediated exclusively through the Y440 motif of the human IFNGR1 receptor subunit. Contrary to this accepted dogma, here it is shown that IFNGR1 with a mutant (Y440F) motif, when stably expressed in IFNGR1-negative human fibroblasts at levels similar to wild type, can sustain a substantial IFN- response. The mutant receptor supports selective induction of IFN--inducible genes but is notably defective in the CIITA, class II HLA, suppressor of cytokine signaling and antiviral responses. Remarkably, similar selective defects are observed in human fibrosarcoma cells expressing a mutant JAK1. The phenotypes are novel and appear distinct from those observed in response to the inhibition of known additional pathways. Data from different cell types further emphasizes the importance of cellular background in determining the response.

This article has been cited by other articles:

				R. Christova, T. Jones, P.-J. Wu, A. Bolzer, A. P. Costa-Pereira, D. Watling, I. M. Kerr, and D. Sheer P-STAT1 mediates higher-order chromatin remodelling of the human MHC in response to IFN{gamma} J. Cell Sci., September 15, 2007; 120(18): 3262 - 3270. [Abstract] [Full Text] [PDF]