Different epitopes are required for gp130 activation by interleukin‐6, oncostatin M and leukemia inhibitory factor

FEBS Letters

Pflanz, Stefan¹  Grötzinger, Joachim¹  Müller-Newen, Gerhard¹  Timmermann, Andreas¹  Kurth, Ingo¹  Küster, Andrea¹  Heinrich, Peter C.¹  Pitard, Vincent² 

[1] Institut für Biochemie, Rheinisch-Westfälische Technische Hochschule Aachen, Pauwelsstraße 30, D-52057 Aachen, Germany;CNRS-UMR 5540, Fédération de Recherche No. 60, Université de Bordeaux 2, 146 rue Léo-Saignat, 33076 Bordeaux Cedex, France

关键词: gp130;    Cytokine;    Receptor;    Signal transduction;    Ba/F3 cell;    CBM;    cytokine binding module;    D;    domain;    LIF;    leukemia inhibitory factor;    OSM;    oncostatin M;    s;    soluble;    STAT;    signal transducer and activator of transcription;   

DOI  :  10.1016/S0014-5793(00)01205-9

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Gp130 is the common signal transducing receptor subunit of interleukin (IL)-6, IL-11, leukemia inhibitory factor (LIF), oncostatin M (OSM), ciliary neurotrophic factor and cardiotrophin-1. IL-6 and IL-11 induce gp130 homodimerization whereas the others lead to the formation of heterodimers with LIFR or OSMR. Binding epitopes for IL-6 and IL-11 are located in the immunoglobulin-like domain and the cytokine binding module (CBM). Here we show that a gp130 mutant lacking domain 1, although unresponsive to IL-6 and IL-11, can still activate signal transducer and activator of transcription (STAT) transcription factors in response to LIF or OSM. Moreover, point mutations in the CBM of gp130 (F191E and V252D) that severely impair signal transduction in response to IL-6 and IL-11 differentially interfere with gp130 activation in response to LIF and OSM. Thus, epitopes involved in gp130 homodimerization are distinct from those leading to the formation of gp130/LIFR or gp130/OSMR heterodimers. These findings may serve as the base for rational design of gp130 antagonists that specifically interfere with bioactivity of distinct IL-6-type cytokines.

【 授权许可】

Unknown