PMID: 15356148Sep 10, 2004Paper

Characterization of a dipeptide motif regulating IFN-gamma receptor 2 plasma membrane accumulation and IFN-gamma responsiveness

The Journal of Immunology : Official Journal of the American Association of Immunologists
Sergio D RosenzweigS M Holland

Abstract

The IFN-gammaR complex is composed of two IFN-gammaR1 and two IFN-gammaR2 polypeptide chains. Although IFN-gammaR1 is constitutively expressed on all nucleated cells, IFN-gammaR2 membrane display is selective and tightly regulated. We created a series of fluorescent-tagged IFN-gammaR2 expression constructs to follow the molecule's cell surface expression and intracellular distribution. Truncation of the receptor immediately upstream of Leu-Ile 255-256 (254X) created a receptor devoid of signaling that overaccumulated on the cell surface. In addition, this truncated receptor inhibited wild-type IFN-gammaR2 activity and therefore exerted a dominant negative effect. In-frame deletion (255Delta2) or alanine substitution (LI255-256AA) of these amino acids created mutants that overaccumulated on the plasma membrane, but had enhanced function. Single amino acid substitutions (L255A or I256A) had a more modest effect. In-frame deletions upstream (253Delta2), but not downstream (257Delta2), of Leu-Ile 255-256 also led to overaccumulation. A truncation within the IFN-gammaR2 Jak2 binding site (270X) led to a mutant devoid of function that did not overaccumulate and did not affect wild-type IFN-gammaR2 signaling. We have created a series ...Continue Reading

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Citations

May 4, 2006·The Journal of Immunology : Official Journal of the American Association of Immunologists·Carlos LeonNeil E Reiner
May 19, 2012·Journal of Leukocyte Biology·Judith YancoskiSergio D Rosenzweig
Sep 10, 2004·The Journal of Immunology : Official Journal of the American Association of Immunologists·Sergio D RosenzweigSteven M Holland
Nov 5, 2010·The Journal of Immunology : Official Journal of the American Association of Immunologists·Dina AggadMaria Leptin
Jan 22, 2005·Immunological Reviews·Sergio D Rosenzweig, Steven M Holland
Mar 6, 2018·Critical Reviews in Clinical Laboratory Sciences·Ana Esteve-SoléJacinta Bustamante
Apr 19, 2006·Cancer Research·Marina N TorreroShulin Li
Dec 29, 2005·Trends in Immunology·Gabriella RegisFrancesco Novelli
May 12, 2007·Biochimie·Julie ClaudinonChristophe Lamaze
Jun 21, 2017·Biochimica Et Biophysica Acta. Molecular Cell Research·Juliane LokauChristoph Garbers

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