Abstract
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.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Animals
-
Antigens, CD / genetics
-
Antigens, CD / 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
-
Membrane Glycoproteins / 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
Substances
-
Antigens, CD
-
DNA-Binding Proteins
-
Epitopes
-
IL11RA protein, human
-
IL6ST protein, human
-
Interleukin-11
-
Interleukin-11 Receptor alpha Subunit
-
Interleukin-6
-
Membrane Glycoproteins
-
Receptors, Interleukin
-
Receptors, Interleukin-11
-
Receptors, Interleukin-6
-
Recombinant Fusion Proteins
-
Recombinant Proteins
-
STAT1 Transcription Factor
-
STAT1 protein, human
-
STAT3 Transcription Factor
-
STAT3 protein, human
-
Trans-Activators
-
Cytokine Receptor gp130
-
Protein-Tyrosine Kinases