Activation of the signal transducer gp130 by interleukin-11 and interleukin-6 is mediated by similar molecular interactions

被引:68
作者
Dahmen, H
Horsten, U
Küster, A
Jacques, Y
Minvielle, S
Kerr, IM
Ciliberto, G
Paonessa, G
Heinrich, RC
Müller-Newen, G
机构
[1] Rhein Westfal TH Aachen, Inst Biochem, D-52057 Aachen, Germany
[2] Unite INSERM 463, Grp Rech Cytokines & Recepteurs, F-44035 Nantes 1, France
[3] Imperial Canc Res Fund, London WC2A 3PX, England
[4] Inst Ric Biol Mol P Angeletti, Dept Genet, I-00040 Pomezia, Italy
关键词
D O I
10.1042/bj3310695
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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-ll (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-II activate gp130 by very similar molecular mechanisms.
引用
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页码:695 / 702
页数:8
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