Molecular cloning of two isoforms of a receptor for the human hematopoietic cytokine interleukin-11

Abstract

Interleukin-11 (IL-11) is a stromal cell-derived cytokine with multiple biologic activities on lymphohematopoietic cells. It belongs to a family of pleiotropic and redundant cytokines that use the gp 130 transducing subunit in their high affinity receptors. By amplifying human cDNA libraries with oligonucleotide primers corresponding to the conserved WSXWS motif found in the hematopoietic cytokine receptor family, a novel cytokine receptor cDNA was identified that, based on high (82%) sequence homology with the recently cloned murine IL-11 receptor, appears to encode the human IL-11 receptor. This receptor is a 422-amino acid protein containing a signal peptide followed by extracellular, transmembrane, and cytoplasmic domains. The extracellular region has a two-domain structure homologous to those of the IL-6 and ciliary neurotrophic factor (CNTF) receptors: an immunoglobulin-like domain and a cytokine receptor-like domain. In addition, an isoform of the human IL-11 receptor that lacks the cytoplasmic domain was also identified. In agreement with the pleiotropic effects of IL-11 on different hematopoietic lineages and bone cells, IL-11 receptor transcripts were found to be expressed by the myelogenous leukemia cell line K562, the megakaryocytic leukemia cell line Mo7E, the erythroleukemia cell line TF1, and the osteosarcoma cell lines MG-63 and Saos-2.

IL11RA‐related Crouzon‐like autosomal recessive craniosynostosis in 10 new patients: Resemblances and differences

“…IL11RA encodes an interleukin 11 receptor alpha subunit. It interacts with the coreceptor gp130 to form a signaling complex that enables phosphorylation of the intracellular tyrosine of gp130 . It allows balanced interactions between osteoblasts precursors and osteoclasts, hence promoting direct intramembranous ossification without cartilaginous template .…”

Alanine Substitution for Thr268 and Asp269 of Soluble Ciliary Neurotrophic Factor (CNTF) Receptor α Component Defines a Specific Antagonist for the CNTF Response

“…A binding subunit for IL-11 displaying a similar homology level to IL-6R␣ and CNTFR␣ was recently isolated in the mouse and human (Hilton et al, 1994;Cherel et al, 1995). Since gp130 is also involved in the transducing machinery of IL-11, we aligned the amino acid sequences of CNTFR␣ and IL-11R␣.…”

“…CNTFR␣ shows 50 and 54% homology with the IL-6 receptor ␣ (IL-6R␣) and with the IL-11 receptor ␣ (IL-11R␣), respectively (Yamasaki et al, 1988;Hilton et al, 1994;Cherel et al, 1995). Two regions of the IL-6R␣ involved in its association with gp130 are conserved in the IL-11 and CNTF receptor ␣ subunits.…”

A fusion protein of interleukin‐11 and soluble interleukin‐11 receptor acts as a superagonist on cells expressing gp130

“…IL‐11 belongs to a subfamily of the 4‐helix bundle cytokines including interleukin‐6 (IL‐6), leukemia inhibitory factor (LIF), oncostatin M (OSM), ciliary neurotrophic factor (CNTF) and cardiotrophin‐1 (CT‐1) that signal via the common signal transducing receptor protein gp130 (for review see [8]). IL‐11 first binds to its specific α‐receptor subunit (IL‐11R) [9,10] and subsequently, the complex of IL‐11 and IL‐11R triggers the dimerization of gp130 [11] leading to activation of the Janus kinase (Jak)/signal transducer and activator of transcription (STAT) signal transduction pathway [12]. Both receptor components belong to the family of hematopoietic cytokine receptors which are characterized by the presence of at least one cytokine binding module (CBM) [13].…”

“…The extracellular part of the IL‐11R is proposed to consist of an Ig‐like domain (D1) followed by a single CBM (D2 and D3) [9]. Whereas gp130 is expressed ubiquitously [14], IL‐11R expression is more restricted [9,10]. Cells expressing gp130 but lacking membrane‐bound IL‐11R can be stimulated by the combination of IL‐11 and soluble IL‐11R (sIL‐11R) indicating that the cytoplasmic and transmembrane parts of IL‐11R are not required for signal transduction [15].…”