Document Detail


Activation of the signal transducer gp130 by interleukin-11 and interleukin-6 is mediated by similar molecular interactions.
MedLine Citation:
PMID:  9560294     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The transmembrane glycoprotein gp130 is involved in many cytokine-mediated cellular responses and acts therein as the signal transducing receptor subunit. Interleukin-6 (IL-6) and interleukin-11 (IL-11), in complex with their specific alpha-receptors, homodimerize gp130 and, as a consequence, activate the Janus kinase (Jak)/signal transducer and activator of transcription (STAT) signalling pathway in their target cells. So far, it is not clear whether gp130 is bound to these cytokines and their specific alpha-receptor subunits through identical or different epitopes. In order to study the interaction of IL-11 and IL-11R with human gp130 the soluble form of the recently cloned human IL-11R was expressed in baculovirus-infected insect cells. By a coprecipitation binding-assay it is demonstrated that IL-11 and IL-6 compete for binding to gp130. Using deletion and point mutants of gp130 it is shown that IL-11-IL-11R and IL-6-IL-6R recognize overlapping binding motifs on gp130. Moreover, using well-established Jak-deficient cell lines we demonstrate that STAT activation by IL-11 requires Jak1. Taken together, our data support the concept that IL-6 and IL-11 activate gp130 by very similar molecular mechanisms.
Authors:
H Dahmen; U Horsten; A Küster; Y Jacques; S Minvielle; I M Kerr; G Ciliberto; G Paonessa; P C Heinrich; G Müller-Newen
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  The Biochemical journal     Volume:  331 ( Pt 3)     ISSN:  0264-6021     ISO Abbreviation:  Biochem. J.     Publication Date:  1998 May 
Date Detail:
Created Date:  1998-10-26     Completed Date:  1998-10-26     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  2984726R     Medline TA:  Biochem J     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  695-702     Citation Subset:  IM    
Affiliation:
Institut für Biochemie, Rheinisch-Westfälische Technische Hochschule Aachen, Pauwelsstr. 30, D-52057 Aachen, Germany.
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MeSH Terms
Descriptor/Qualifier:
Animals
Antigens, CD / genetics,  metabolism*
Binding, Competitive / physiology
Cell Division / drug effects
Cell Line
Cytokine Receptor gp130
DNA-Binding Proteins / metabolism
Dimerization
Epitopes / immunology
Humans
Interleukin-11 / pharmacology*
Interleukin-11 Receptor alpha Subunit
Interleukin-6 / pharmacology*
Membrane Glycoproteins / genetics,  metabolism*
Mutation / genetics
Protein-Tyrosine Kinases / metabolism
Receptors, Interleukin / metabolism
Receptors, Interleukin-11
Receptors, Interleukin-6 / metabolism
Recombinant Fusion Proteins / metabolism
Recombinant Proteins / metabolism
STAT1 Transcription Factor
STAT3 Transcription Factor
Signal Transduction / physiology*
Trans-Activators / metabolism
Chemical
Reg. No./Substance:
0/Antigens, CD; 0/DNA-Binding Proteins; 0/Epitopes; 0/IL11RA protein, human; 0/IL6ST protein, human; 0/Interleukin-11; 0/Interleukin-11 Receptor alpha Subunit; 0/Interleukin-6; 0/Membrane Glycoproteins; 0/Receptors, Interleukin; 0/Receptors, Interleukin-11; 0/Receptors, Interleukin-6; 0/Recombinant Fusion Proteins; 0/Recombinant Proteins; 0/STAT1 Transcription Factor; 0/STAT1 protein, human; 0/STAT3 Transcription Factor; 0/STAT3 protein, human; 0/Trans-Activators; 133483-10-0/Cytokine Receptor gp130; EC 2.7.10.1/Protein-Tyrosine Kinases
Comments/Corrections

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