Activation of the signal transducer gp130 by interleukin-11 and interleukin-6 is mediated by similar molecular interactions.
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.
Dahmen
H
H
Institut für Biochemie, Rheinisch-Westfälische Technische Hochschule Aachen, Pauwelsstr. 30, D-52057 Aachen, Germany.
Horsten
U
U
Küster
A
A
Jacques
Y
Y
Minvielle
S
S
Kerr
I M
IM
Ciliberto
G
G
Paonessa
G
G
Heinrich
P C
PC
Müller-Newen
G
G
D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism*; D001667:Binding, Competitive / Q000502:physiology; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D050822:Cytokine Receptor gp130; D004268:DNA-Binding Proteins / Q000378:metabolism; D019281:Dimerization; D000939:Epitopes / Q000276:immunology; D006801:Humans; D017370:Interleukin-11 / Q000494:pharmacology*; D053703:Interleukin-11 Receptor alpha Subunit; D015850:Interleukin-6 / Q000494:pharmacology*; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism*; D009154:Mutation / Q000235:genetics; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D018123:Receptors, Interleukin / Q000378:metabolism; D053702:Receptors, Interleukin-11; D019947:Receptors, Interleukin-6 / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism; D050794:STAT1 Transcription Factor; D050796:STAT3 Transcription Factor; D015398:Signal Transduction / Q000502:physiology*; D015534:Trans-Activators / Q000378:metabolism
D015703:Antigens, CD; D004268:DNA-Binding Proteins; D000939:Epitopes; C508428:IL11RA protein, human; C494199:IL6ST protein, human; D017370:Interleukin-11; D053703:Interleukin-11 Receptor alpha Subunit; D015850:Interleukin-6; D008562:Membrane Glycoproteins; D018123:Receptors, Interleukin; D053702:Receptors, Interleukin-11; D019947:Receptors, Interleukin-6; D011993:Recombinant Fusion Proteins; D011994:Recombinant Proteins; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D015534:Trans-Activators; D050822:Cytokine Receptor gp130; D011505:Protein-Tyrosine Kinases