A Novel Type I Cytokine Receptor Is Expressed on Monocytes, Signals Proliferation, and Activates STAT-3 and STAT-5

Ghilardi, Nico; Li, Ji; Hongo, Jo-Anne; Yi, Sothy; Gurney, Austin; Sauvage, Frédéric J. de

doi:10.1074/jbc.m201140200

Cited by 70 publications

(68 citation statements)

References 33 publications

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“…Results show that a self-dimerization process of GPL led to no or to a marginal functional response, in contrast to that reported before (24). Interestingly, GPL can contact and recruit LIFR or gp130 intracellular portions.…”

Section: Discussioncontrasting

confidence: 54%

“…This receptor is structurally related to the receptors for the long-chain cytokines encompassing the IL-6/IL-12 type cytokines and granulocyte-colony stimulating factor (8 -11, 14, 20, 48, 49). A recent study reported a partial sequence of a similar receptor (24). But the absence of a large portion of the leader sequence did not allow expression of any corresponding protein, rendering its subsequent functional analysis difficult.…”

Section: Discussionmentioning

confidence: 99%

“…A related receptor was described recently, but the reported sequence was incomplete, thus preventing expression of the corresponding protein (24). This receptor we named GPL, for GP130 Like receptor, which displayed some homologies with LIFR, OSMR, and the IL-12 receptor family members.…”

mentioning

confidence: 99%

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

Diveu

Lelièvre

Perret

et al. 2003

Journal of Biological Chemistry

105

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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.

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Section: Discussioncontrasting

confidence: 54%

Section: Discussionmentioning

confidence: 99%

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

Diveu

Lelièvre

Perret

et al. 2003

Journal of Biological Chemistry

105

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“…The IL-31 heterodimeric receptor is composed of gp130-like receptor (GPL, also known as GLM-R or IL-31RA) (1,10,11) and oncostatin M receptor (OSMR) (12,13). GPL was cloned as a member of the type I cytokine receptor family (10,11).…”

Section: Interleukin-31 (Il-31)mentioning

confidence: 99%

Molecular Dissection of Human Interleukin-31-mediated Signal Transduction through Site-directed Mutagenesis

Saux¹,

Rousseau²,

Barbier³

et al. 2010

Journal of Biological Chemistry

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Interleukin (IL)-31 is a recently described cytokine, preferentially produced by T helper 2 lymphocytes and associated with skin diseases, such as atopic dermatitis. IL-31 is a member of the four ␣-helix bundle cytokine family and is related to the IL-6 subgroup. Its heterodimeric membrane receptor is composed of the gp130-like receptor (GPL) subunit associated to the oncostatin M receptor subunit. We identified critical amino acids implicated in the ligand receptor interaction by computational analysis combined with site-directed mutagenesis. Six IL-31 residues selected for their putative involvement in cytokine receptor contact sites were alanine-substituted, and the corresponding proteins were expressed in mammalian and bacterial systems. Biochemical, membrane binding, cell signaling, and cell proliferation analyses showed that mutation E44A, E106A, or H110A abolished IL-31 binding to GPL and the subsequent signaling events. A second ligand receptor-binding site involved Lys 134 , with alanine substitution leading to a protein that still binds GPL, but is unable to recruit the second receptor subunit and the subsequent signaling pathways. The results indicate that IL-31 recognizes its receptor complex through two different binding sites, and we propose a three-dimensional model for IL-31. 4 is a newly described T cell-derived cytokine mostly produced by T helper type 2 cells and involved in promoting skin disorders and regulating other allergic diseases such as asthma (1-5). Mice treated with intradermal injection of IL-31 or transgenic mice overexpressing IL-31 present increased scratching behavior and develop severe dermatitis (1). An association of IL-31 with atopic dermatitis was found in the IL-31 transgenic mouse phenotype that mimics the human pathology (6).In humans, atopic individuals have an increased tendency to produce high levels of IL-31 in response to external trigger factors, which may contribute to the development of pruritus. Moreover, IL-31 mRNA is increased in circulating and skininfiltrating cutaneous lymphocyte antigen-positive T cells of these patients (7). This cytokine is related to the IL-6 cytokine family by its structure and receptor complex (8). IL-31 is a fourhelix bundle cytokine comprising two long cross-over loops and one short loop (1, 9). The mRNA encodes for a 15.5-kDa protein displaying an apparent molecular mass of 24 kDa in its glycosylated form. Based on its overall length, IL-31 is quite close to the IL-2 or granulocyte colony-stimulating factor short chain groups of cytokines but does not display apparent homology or functional properties with them.The IL-31 heterodimeric receptor is composed of gp130-like receptor (GPL, also known as GLM-R or IL-31RA) (1, 10, 11) and oncostatin M receptor (OSMR) (12, 13). GPL was cloned as a member of the type I cytokine receptor family (10, 11). Its name reflects its close homology to gp130, the shared receptor subunit of the IL-6-type cytokines (14, 15). GPL displays common structural motifs with the family of type I cytokine rece...

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“…from the C T value for ribosomal protein L19 (RPL19), which serves as an internal control (24,25). All reactions were run in duplicates.…”

Section: Fig 2 Effect Of Mpl-tr On Proliferation Of Cytokine-dependmentioning

confidence: 99%

A Truncated Isoform of c-Mpl with an Essential C-terminal Peptide Targets the Full-length Receptor for Degradation

Coers

Ranft

Skoda

2004

Journal of Biological Chemistry

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A Novel Type I Cytokine Receptor Is Expressed on Monocytes, Signals Proliferation, and Activates STAT-3 and STAT-5

Cited by 70 publications

References 33 publications

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

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

Molecular Dissection of Human Interleukin-31-mediated Signal Transduction through Site-directed Mutagenesis

A Truncated Isoform of c-Mpl with an Essential C-terminal Peptide Targets the Full-length Receptor for Degradation

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