The human IL-11 receptor requires gp130 for signalling: Demonstration by molecular cloning of the receptor
- Author(s)
- Nandurkar, HH; Hilton, DJ; Nathan, P; Willson, T; Nicola, N; Begley, CG;
- Details
- Publication Year 1996-02-01,Volume 12,Issue #3,Page 585-593
- Journal Title
- ONCOGENE
- Publication Type
- Journal Article
- 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 (K-d=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.
- Publisher
- STOCKTON PRESS
- Keywords
- COLONY-STIMULATING FACTOR; LEUKEMIA-INHIBITORY FACTOR; MURINE HEMATOPOIETIC-CELLS; EXPRESSION CLONING; GM-CSF; CYTOKINE RECEPTORS; RECOMBINANT INTERLEUKIN-11; SYNERGISTIC INTERACTIONS; MARROW CULTURES; SOLUBLE FORM
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Creation Date: 1996-02-01 12:00:00