GPL, a Novel Cytokine Receptor Related to GP130 and Leukemia Inhibitory Factor Receptor

Abstract

We describe a novel cytokine receptor named GP130 Like receptor, or GPL, that displays similarities with the interleukin-6 and interleukin-12 family of signaling receptors. Four different isoforms diverging in their carboxyl terminus were isolated, corresponding to proteins encompassing 560, 610, 626, and 745 amino acids. Sequences included a signal peptide of 32 amino acids, followed by a cytokine binding domain containing four conserved cysteines, a WSDWS motif, and a region consisting of three fibronectin type III domain repeats. No immunoglobulin-like module was identified in the GPL sequences. The intracellular part of longer isoforms contained a proline-rich region defining a box1 motif for interaction with the Janus kinases. The Gpl gene is organized in 15 exons and is located on 5q11.2 in tandem with the gp130 gene. Both genes were only separated by 24 kilobases, with opposite transcriptional orientations. The GPL receptor displayed a 28% identity with gp130. Specific GPL transcripts were observed in tissues involved in reproduction. Transcripts were also found in blood cells and in bone marrow, revealing expression of GPL in all of the myelomonocytic lineage, from hematopoietic stem cells to activated dendritic cells. In monocytes and dendritic cells, expression of GPL was strongly up-regulated by interferon-␥, indicating a possible involvement of GPL in Th1-type immune responses. The molecular basis of cell signaling mediated by GPL was studied using chimeric receptors where external portions of ␣ or ␤ interleukin-5 receptor subunits were fused to the internal portion of GPL or of related receptors. Results indicated that association of GPL to the intracellular portions of gp130, or LIF receptor, allowed the signaling cascade.

Molecular and Functional Characterization of a Soluble Form of Oncostatin M/Interleukin-31 Shared Receptor

“…Recent studies from Zymogenetics researchers and from our group reported that OSMR also associate to a gp130-like receptor, GPL or IL-31R, to generate a functional receptor for IL-31 (32)(33)(34). In the present study we have shown that sOSMR together with GPL/IL-31R could also neutralize IL-31.…”

“…8B). Recent studies have demonstrated the OSMR involvement, together with Gp130-like receptor (GPL), also known as IL-31R, in the formation of a functional IL-31 receptor complex (32)(33)(34). We tested the possibility for sOSMR to also neutralize an IL-31 response in the T98G glioblastoma cell line (Fig.…”

“…In addition, OSM potently induces the proliferation of Kaposi sarcoma, fibroblastic, and smooth muscle cells (29 -31). It was recently reported that OSMR could also be recruited by IL-31, a novel cytokine with a skin tropism (32)(33)(34).…”

Interleukin-31 and Oncostatin-M Mediate Distinct Signaling Reactions and Response Patterns in Lung Epithelial Cells

“…Cytokine and Cytokine Receptor Constructs-The proteincoding region for human IL-31 and the long form (745 amino acids) IL-31R␣ was identified in the genome data bank based on the published sequence (14,15). The IL-31 cDNA (encoding amino acid residues 24 -164, NCBI accession number NP001014358.1) was generated by reverse transcription-PCR using RNA from mitogen-activated human peripheral T-cells.…”

“…14) as a member of the IL-6R group that does not engage gp130, but OSMR␤, to form a signaling receptor complex (15,16). Based on the effects of ectopic expression in transgenic mice, IL-31, a CD4 ϩ T-cell-derived cytokine, has been associated with pruritis and dermatitis affecting dermal keratinocytes and dorsal root ganglia (17)(18)(19).…”