Reactome: A Curated Pathway Database

Assembly of a hexameric IL-6 receptor

Stable Identifier
R-HSA-1067659
Type
Reaction
Species
Homo sapiens
Compartment
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Summation

There are three contact sites between IL-6, IL-6R and gp130, named site I, II and III. Site I and II correspond to the respective sites of the growth hormone receptor complex whereas site III is only found in receptor complexes with at least three subunits. Various models of the IL-6 receptor complex have been proposed (Scheller & Rose-John 2006), but crystallographic data suggests the assembly of a hexameric complex containing two IL-6, two IL-6RA and two gp130 subunits. It has been argued that the minimal signalling complex is one IL6:IL6R complex bound to two gp130 proteins (Grotzinger et al. 1999). The quaternary structures of other IL-6/IL-12 family signaling complexes suggest they have a similar topology (Boulanger et al. 2003). IL-6 binding is achieved by the cytokine-binding and the immunglobulin-like domains (Boulanger et al. 2003). The gp130 fibronectin-like domains are thought to position the transmembrane domains of the paired gp130 receptor complexes in close proximity and thereby induce signaling (Skiniotis et al. 2005). Forced dimerization of gp130 with itself or the related Interleukin-27 receptor subunit alpha (WSX-1), Leukemia inhibitory factor receptor or Oncostatin M receptors led to constitutive, ligand-independent STAT1 and/or STAT3 activation and ERK1/2 phosphorylation, suggesting that all heterodimeric gp130-type receptor complexes are activated by a similar mechanism in which close juxtaposition of the intracellular receptor domains is sufficient for signal induction (Suthaus et al. 2010).

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