Identification of a Cys motif in the common beta chain of the interleukin 3, granulocyte-macrophage colony-stimulating factor, and interleukin 5 receptors essential for disulfide-linked receptor heterodimerization and activation of all three receptors.

The Journal of Biological Chemistry
F C StomskiA F Lopez

Abstract

The human interleukin 3 (IL-3) and granulocyte-macrophage colony-stimulating factor (GM-CSF) receptors undergo covalent dimerization of the respective specific alpha chains with the common beta subunit (betac) in the presence of the cognate ligand. We have now performed alanine substitutions of individual Cys residues in betac to identify the Cys residues involved and their contribution to activation of the IL-3, GM-CSF, and IL-5 receptors. We found that substitution of Cys-86, Cys-91, and Cys-96 in betac but not of Cys-100 or Cys-234 abrogated disulfide-linked IL-3 receptor dimerization. However, although Cys-86 and Cys-91 betac mutants retained their ability to form non-disulfide-linked dimers with IL-3Ralpha, substitution of Cys-96 eliminated this interaction. Binding studies demonstrated that all betac mutants with the exception of C96A supported high affinity binding of IL-3 and GM-CSF. In receptor activation experiments, we found that betac mutants C86A, C91A, and C96A but not C100A or C234A abolished phosphorylation of betac in response to IL-3, GM-CSF, or IL-5. These data show that although Cys-96 is important for the structural integrity of betac, Cys-86 and Cys-91 participate in disulfide-linked receptor heterodimeriz...Continue Reading

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Citations

Apr 12, 2001·European Journal of Immunology·L ZabeauJ Tavernier
Mar 29, 2013·Cytokine & Growth Factor Reviews·Timothy R HercusAngel F Lopez
Oct 18, 2003·The Journal of Allergy and Clinical Immunology·Margarita Martinez-Moczygemba, David P Huston
May 5, 1999·Annals of Allergy, Asthma & Immunology : Official Publication of the American College of Allergy, Asthma, & Immunology·T LalaniA R Ahmed
Mar 11, 2008·The Journal of Biological Chemistry·Meirav Zaks-ZilbermanIrwin M Chaiken
Jul 31, 2012·Critical Care : the Official Journal of the Critical Care Forum·Nimesh S A PatelChristoph Thiemermann
Dec 21, 2011·Molecular Medicine·Michael Brines, Anthony Cerami
Aug 7, 2014·Proceedings of the National Academy of Sciences of the United States of America·Sonia SalzanoPietro Ghezzi
Jun 12, 2010·IUBMB Life·Angel F LopezMichael W Parker
Oct 9, 2012·European Journal of Immunology·David Voehringer
Oct 11, 2012·Immunological Reviews·Sophie E BroughtonMichael W Parker
Apr 21, 2005·The Journal of Biological Chemistry·Lennart ZabeauJan Tavernier
Jan 20, 2017·Microbiology Spectrum·Mark M HughesLuke A J O'Neill

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