The human IL-11 receptor requires gp130 for signalling: demonstration by molecular cloning of the receptor.

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Nandurkar HH, Hilton DJ, Nathan P, Willson T, Nicola N, Begley CG

The human IL-11 receptor requires gp130 for signalling: demonstration by molecular cloning of the receptor.

Oncogene. 1996 Feb 1;12(3):585-93.

PubMed ID

8637716 [ View in PubMed

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Abstract

We describe the molecular cloning of a cDNA for the alpha chain of the human IL-11 receptor (IL-11R alpha) and demonstrate the requirement of either the human or mouse gp130 molecule for signalling. cDNA clones encoding IL-11R alpha were isolated from a bone marrow cDNA library using a fragment from the murine IL-11R alpha as a probe. The human receptor was predicted to consist of 422 amino acids and was found to share 84% identity with the murine protein. In the extra-cellular region it exhibited a single hemopoietin domain with conserved cysteine residues and WSTWS motif. The transmembrane region was followed by a short cytoplasmic tail which did not contain a tyrosine kinase domain. Interaction of the human IL-11R alpha with murine gp130 was demonstrated: expression of the human IL-11R alpha in murine M1 cells which constitutively express murine gp130 (and murine LIF receptor), resulted in the generation of specific high-affinity binding sites for IL-11 (Kd = 250 pM). In addition, expression of the human IL-11R alpha in these cells permitted the induction of macrophage differentiation in response to IL-11. These results suggested that the human IL-11R alpha chain was able to form a functional receptor complex in association with murine gp130. The requirement of gp130 for signalling was confirmed by expression of the human IL-11R alpha in Ba/F3 cells. BaF3 cells that expressed the human IL-11R alpha alone showed binding of radiolabelled IL-11 but no proliferative response. Introduction of human gp130 into these cells resulted in high-affinity IL-11 binding sites and IL-11 dependent cellular proliferation. Thus these results demonstrated the absolute requirement of gp130 for signalling.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Oprelvekin	Interleukin-11 receptor subunit alpha	Protein	Humans	Yes	Agonist	Details