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

Harshal Hanumant Nandurkar, Douglas James Hilton, Paula Nathan, Tracy A Willson, Nicos A Nicola, Colin Glenn Begley

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Abstract

We describe the molecular cloning of a cDNA for the a chain of the human IL-11 receptor (IL-11Ra) and demonstrate the requirement of either the human or mouse gp130 molecule for signalling. cDNA clones encoding IL-11Ra were isolated from a bone marrow cDNA library using a fragment from the murine IL-11Ra 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-11Ra with murine gp130 was demonstrated: expression of the human IL-11Ra 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 (K(d) = 250 pM). In addition, expression of the human IL-11Ra in these cells permitted the induction of macrophage differentiation in response to IL-11. These results suggested that the human IL-11Ra 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-11Ra in Ba/F3 cells. BaF3 cells that expressed the human IL-11Ra 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.
Original languageEnglish
Pages (from-to)585 - 593
Number of pages9
JournalOncogene
Volume12
Issue number3
Publication statusPublished - 1996
Externally publishedYes

Cite this

Nandurkar, H. H., Hilton, D. J., Nathan, P., Willson, T. A., Nicola, N. A., & Begley, C. G. (1996). The human IL-11 receptor requires gp130 for signalling: Demonstration by molecular cloning of the receptor. Oncogene, 12(3), 585 - 593.