A single amino acid substitution (Trp(666)-->Ala) in the interbox1/2 region of the interleukin-6 signal transducer gp130 abrogates binding of JAK1, and dominantly impairs signal transduction

Haan, Claude; Hermanns, H. M.; Heinrich, P. C.; Behrmann, Iris

Reference : A single amino acid substitution (Trp(666)-->Ala) in the interbox1/2 region of the in...


	Document type :	Scientific journals : Article
	Discipline(s) :	Life sciences : Biochemistry, biophysics & molecular biology
	To cite this reference:	http://hdl.handle.net/10993/6243

Title :	A single amino acid substitution (Trp(666)-->Ala) in the interbox1/2 region of the interleukin-6 signal transducer gp130 abrogates binding of JAK1, and dominantly impairs signal transduction
Language :	English
Author, co-author :	Haan, Claude [University of Luxembourg > Faculty of Science, Technology and Communication (FSTC) > Life Science Research Unit >]
	Hermanns, H. M. [> >]
	Heinrich, P. C. [> >]
	Behrmann, Iris [University of Luxembourg > Faculty of Science, Technology and Communication (FSTC) > Life Science Research Unit >]
Publication date :	2001
Journal title :	Biochemical Journal
Publisher :	Portland Press
Volume :	349
Issue/season :	Pt 1
Pages :	261-6
Peer reviewed :	Yes (verified by ORBi^lu)
Audience :	International
ISSN :	0264-6021
e-ISSN :	1470-8728
City :	London
Country :	United Kingdom
Keywords :	[en] Alanine ; Mutagenesis, Site-Directed ; Point Mutation ; Protein Binding ; Protein Structure, Tertiary ; Protein-Tyrosine Kinases ; Receptors, Interleukin ; Receptors, Interleukin-5 ; Signal Transduction ; Trans-Activation (Genetics) ; Transfection ; Mice ; Membrane Glycoproteins ; Animals ; Antigens, CD ; B-Lymphocytes ; COS Cells ; Cell Division ; Cytokine Receptor gp130 ; Cytoplasm ; Dose-Response Relationship, Drug ; Interleukin-6 ; Janus Kinase 1 ; Tryptophan
Abstract :	[en] gp130 is the common signal-transducing receptor chain of interleukin (IL)-6-type cytokines. Here we describe, for the first time, a single amino acid substitution (Trp(666)-->Ala) in the membrane-proximal interbox1/2 region that abrogates activation of STAT (signal transducer and activator of transcription) transcription factors and the proliferative response of pro-B-cell transfectants. Moreover, association of the Janus kinase JAK1 is prevented. No signalling of heterodimeric IL-5 receptor (IL-5R)/gp130 chimaeras occurs in COS-7 cells, even when only a single cytoplasmic chain of a gp130 dimer contains the Trp(666)Ala mutation, indicating that it acts dominantly.
Permalink :	http://hdl.handle.net/10993/6243

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