Molecular dissection of human interleukin-31-mediated signal transduction through site-directed mutagenesis.

The Journal of Biological Chemistry
Sabine Le SauxH Gascan

Abstract

Interleukin (IL)-31 is a recently described cytokine, preferentially produced by T helper 2 lymphocytes and associated with skin diseases, such as atopic dermatitis. IL-31 is a member of the four alpha-helix bundle cytokine family and is related to the IL-6 subgroup. Its heterodimeric membrane receptor is composed of the gp130-like receptor (GPL) subunit associated to the oncostatin M receptor subunit. We identified critical amino acids implicated in the ligand receptor interaction by computational analysis combined with site-directed mutagenesis. Six IL-31 residues selected for their putative involvement in cytokine receptor contact sites were alanine-substituted, and the corresponding proteins were expressed in mammalian and bacterial systems. Biochemical, membrane binding, cell signaling, and cell proliferation analyses showed that mutation E44A, E106A, or H110A abolished IL-31 binding to GPL and the subsequent signaling events. A second ligand receptor-binding site involved Lys(134), with alanine substitution leading to a protein that still binds GPL, but is unable to recruit the second receptor subunit and the subsequent signaling pathways. The results indicate that IL-31 recognizes its receptor complex through two differe...Continue Reading

References

Sep 1, 1990·Proceedings of the National Academy of Sciences of the United States of America·J F Bazan
Oct 1, 1990·Immunology Today·J F Bazan
Mar 15, 1994·Structure·D A RozwarskiP A Karplus
Aug 20, 1996·Proceedings of the National Academy of Sciences of the United States of America·A Di MarcoR Laufer
Jun 3, 2000·The EMBO Journal·J Bravo, J K Heath
Mar 6, 2002·The Journal of Biological Chemistry·Nico GhilardiFrederic J de Sauvage
Jan 18, 2003·Lancet·Donald Y M Leung, Thomas Bieber
May 30, 2003·The Biochemical Journal·Peter C HeinrichFred Schaper
Jun 28, 2003·Science·Martin J BoulangerK Christopher Garcia
Sep 25, 2003·The Journal of Biological Chemistry·Caroline DiveuAlain Morel
Oct 7, 2003·Molecular Cell·Martin J BoulangerK Christopher Garcia
Jun 9, 2004·Nature Immunology·Stacey R DillonJane A Gross
Jun 15, 2004·The Journal of Biological Chemistry·Alexandra DreuwHeike M Hermanns
Oct 27, 2004·Advances in Protein Chemistry·Martin J Boulanger, K Christopher Garcia
Jun 1, 2005·European Journal of Pharmacology·Akiko TakaokaShiro Nakaike
Feb 8, 2006·The Journal of Allergy and Clinical Immunology·Eniko SonkolyBernhard Homey
Feb 8, 2006·The Journal of Allergy and Clinical Immunology·Janine BilsboroughJane A Gross
Feb 17, 2006·Experimental Dermatology·A TakaokaS Nakaike
Oct 13, 2006·The Journal of Allergy and Clinical Immunology·Mark M NeisHeike M Hermanns
Dec 7, 2006·The Journal of Biological Chemistry·Souvik ChattopadhyayHeinz Baumann
Jul 27, 2007·Proceedings of the National Academy of Sciences of the United States of America·Trevor HuytonThomas P J Garrett
Sep 29, 2007·The Journal of Allergy and Clinical Immunology·Florian SchulzYoung-Ae Lee
Apr 29, 2008·Journal of Interferon & Cytokine Research : the Official Journal of the International Society for Interferon and Cytokine Research·Randeep S JawaHeinz Baumann
Sep 9, 2008·Molecular Cell·Georgios SkiniotisK Christopher Garcia
Sep 27, 2008·Annual Review of Immunology·Xinquan WangK Christopher Garcia
Nov 27, 2008·Nucleic Acids Research·T J P HubbardP Flicek

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Citations

Jul 23, 2015·Cytokine & Growth Factor Reviews·Heike M Hermanns
Oct 1, 2011·European Journal of Cell Biology·Dieter Schwache, Gerhard Müller-Newen
Oct 11, 2011·European Journal of Cell Biology·Christian CornelissenBernhard Lüscher
Mar 8, 2011·The Journal of Allergy and Clinical Immunology·Mübeccel AkdisCezmi A Akdis
Feb 2, 2017·The Journal of Dermatological Treatment·Mohammed D SaleemSteven R Feldman
Aug 18, 2018·Journal of Pathology and Translational Medicine·Mi Young LeeYounghee Choi
Mar 26, 2010·The Journal of Biological Chemistry·Emilie VenereauHugues Gascan
Jan 18, 2015·The Journal of Immunology : Official Journal of the American Association of Immunologists·Ji Sun HwangSin-Hyeog Im
Apr 28, 2012·The Journal of Immunology : Official Journal of the American Association of Immunologists·Jutta Horejs-HoeckAlbert Duschl
May 28, 2020·Biochemistry·Angelica V Medina-CucurellaTimothy A Whitehead

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