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Proliferation and Differentiation of Murine Myeloid Precursor 32D/G-CSF-R Cells
Published on: February 21, 2018
GPL, a novel cytokine receptor related to GP130 and leukemia inhibitory factor receptor
Caroline Diveu1, Eric Lelièvre, David Perret
1INSERM U564, CHU d'Angers, 49033 Angers, France.
Insights
A novel cytokine receptor, GP130 Like receptor (GPL), was identified with similarities to IL-6 and IL-12 receptors. GPL expression in immune cells suggests a role in Th1 immune responses and cell signaling.
Area of Science:
- Immunology
- Molecular Biology
- Genetics
Background:
- Cytokine receptors are crucial for cell signaling in the immune system.
- The interleukin-6 (IL-6) and interleukin-12 (IL-12) families mediate diverse cellular responses.
- Understanding novel cytokine receptors can elucidate new signaling pathways.
Purpose of the Study:
- To identify and characterize a novel cytokine receptor.
- To investigate the structure, gene organization, and expression patterns of the new receptor.
- To explore the functional role of the novel receptor in immune cell signaling.
Main Methods:
- Isolation and sequencing of four GPL isoforms.
- Analysis of gene structure, localization, and homology to known receptors.
- Detection of GPL transcripts in various tissues and cell types.
- Functional studies using chimeric receptors to investigate signaling pathways.
Main Results:
- A novel cytokine receptor, GP130 Like receptor (GPL), was identified with structural similarities to IL-6 and IL-12 receptors.
- Four GPL isoforms were characterized, featuring a cytokine binding domain and intracellular Janus kinase interaction motifs.
- GPL gene is located on chromosome 5q11.2, adjacent to the gp130 gene.
- GPL transcripts were detected in reproductive tissues, blood cells, and the myelomonocytic lineage, with expression upregulated by interferon-gamma in monocytes and dendritic cells.
- Chimeric receptor studies demonstrated that GPL associates with gp130 or LIF receptor intracellular domains to initiate signaling cascades.
Conclusions:
- GPL represents a novel cytokine receptor with potential roles in reproduction and immune responses.
- Its expression pattern and regulation by interferon-gamma suggest involvement in Th1-type immune responses.
- GPL contributes to cell signaling pathways through its interaction with intracellular signaling molecules like Janus kinases.
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-gamma, 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 alpha or beta 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.
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