Synonyms for osmr or Related words with osmr


Examples of "osmr"
LIFR and OSMR also contain the membrane-proximal box1/box2-like regions. The first 65 amino acid residues in the cytoplasmic domain of LIFR, in combination with full length gp130, can generate signalling on treatment with LIF. Coprecipitation of Jak1, Jak2 and Tyk2 with receptors containing cytoplasmic parts of the LIFR or OSMR. All beta receptor subunits of the gp130 system also possess a box 3 region. This region corresponds to the C-terminal amino acids of the OSMR and LIFR receptors respectively. Box 3 is necessary for the action of OSMR; however Box3 is dispensable for the action of LIFR. In the case of gp130 box 3 is dispensable for activity, however the presence of an intact box 3 sequence is required for certain aspects of gp130 signalling, i.e. stimulation of transcription through the STAT-3 response element. In addition to the poor sequence conservation amongst the intracellular domains of gp130 receptors, the number and position of conserved tyrosine residues are also poorly conserved. For example, LIFR and OSMR share three homologous tyrosines. In contrast none of the tyrosine residues present in the intracellular domain of gp130 share equivalents with LIFR or OSMR, even though the intracellular regions of LIFR and gp130 share more sequence identity than LIFR and OSMR.
OSM signals through cell surface receptors that contain the protein gp130. The type I receptor is composed of gp130 and LIFR, the type II receptor is composed of gp130 and OSMR.
OSM is a major growth factor for Kaposi’s sarcoma “spindle cells”, which are of endothelial origin. These cells do not express LIFR but do express OSMR at high levels.
IL-31 signals via a receptor complex that is composed of IL-31 receptor A (IL31RA) and oncostatin M receptor (OSMR) subunits. These receptor subunits are expressed in activated monocytes and in unstimulated epithelial cells. IL-31RA binds IL-31 through its cytokine binding domain (CBD). OSMR does not normally bind to IL-31 but it does increase the IL-31 binding affinity to IL-31RA. IL-31RA has a intracellular domain that possesses a box1 motif that mediates association with kinases of the JAK family. Additionally, the intracellular portion of the IL-31RA contains tyrosine residues. When IL-31 binds to the receptor complex, JAK kinases are activated which phosphorylate and activate STAT1, STAT3, and STAT5. The OSMR portion of the IL-31 binding complex contains intracellular motifs box1 and box2. This allows for JAK1 and JAK2 to bind, which are recruited once the tyrosine residues on the intracellular domain are phosphorylated. Through these phosphorylation sites, STAT3 and STAT5 are recruited and phosphorylated by JAK1 and JAK2. In addition to STATs, PI3K is recruited, which stimulates the PI3K/AKT signaling pathway. In contrast to IL-31RA, which binds SHP-2, the OSMR interacts with the adaptor protein Shc via the phosphorylated tyrosines on its intracellular domain. Through Shc, the RAS/RAF/MEK/ERK pathway is activated along with the p38 and JNK pathways. When IL-31 binds to the IL-31RA/OSMR complex, the JAK, PI3K/AKT, and ERK signaling pathways are activated. The pathways allow for target genes to be transcribed.
Oncostatin-M specific receptor subunit beta also known as the oncostatin M receptor, is one of the receptor proteins for oncostatin M, that in humans is encoded by the "OSMR" gene.
Of the proteins recruited to type I cytokine receptors STAT proteins remain the best studied. Homodimerisation of gp130 has been shown to phosphorylate and activate both STAT1 and STAT3. gp130 preferentially activates STAT3 which it can do through four STAT3 activation consensus sequences YXXQ: (YRHQ), (YFKQ), Y905 (YLPQ), Y915 (YMPQ). The lower propensity for STAT1 activation may be a reflection of the lower number of STAT1 activation sequences, YZPQ (where X is any residue and Z is any uncharged residue), namely Y905 and Y915. Cytokines that signal via homodimeric complexes of LIFR or OSMR (i.e. devoid of gp130) are currently unknown in nature. However, various investigators have attempted artificial homodimerisation of LIFR and OSMR intracellular domains, with conflicting results, by constructing receptor chimeras that fuse the extracellular domain of one cytokine receptor with the intracellular domain of LIFR or OSMR.
OSMR is a member of the type I cytokine receptor family. This protein heterodimerizes with interleukin 6 signal transducer to form the type II oncostatin M receptor and with interleukin 31 receptor A to form the interleukin 31 receptor, and thus transduces oncostatin M and interleukin 31 induced signaling events.
Scatchard analysis of radio ligand binding data from 125I-OSM binding to a variety of OSM responsive cell lines produced curvilinear graphs which the authors interpreted as the presence of two receptor species, a high affinity form with an approximate dissociation constant Kd of 1-10 pM, and a low affinity form of 0.4-1 nM. Subsequently it was shown that the presence of gp130 alone was sufficient to reproduce the low affinity form of the receptor, and co-transfection of COS-7 cells with LIFR and gp130 produced a high affinity receptor. However further experiments demonstrated that not all actions of OSM could be replicated by LIF, that is certain cells that are irresponsive to LIF would respond to OSM. This data hinted to the existence of an additional ligand specific receptor chain which led to the cloning of OSMR. These two receptor complexes, namely gp130/LIFR and gp130/OSMR, were termed the type I and type II Oncostatin-M receptors.
The murine homologue of OSM was not discovered until 1996, whereas the murine OSMR homologue was not cloned until 1998. Until recently, it was thought that mOSM only signals through the murine type II receptor, namely through mOSMR/mgp130 complexes, because of a low affinity for the type I receptor counterpart. However, it is now known that, in bone at least, mOSM is able to signal through both mOSMR/mgp130 and mLIFR/mgp130.
Signalling by type I and type II OSM receptors have now been shown to be qualitatively distinct. These differences in signaling character, in addition to the tissue distribution profiles of OSMRb and LIFRb, offer another variable in the distinction between the common and specific cellular effects of OSM with respect to LIF. All IL-6 cytokines whether they homo- or heterodimerise gp130 seem to activate JAK1, JAK2 and to a lesser degree Tyk2. It should be noted however that JAK1, JAK2, and tyk2 are not interchangeable in the gp130 system, this has been demonstrated with the use of JAK1, Jak2 or Tyk2 deficient cell lines obtained from mutant mice. Cells from JAK1 deficient mice show reduced STAT activation and generation of biological responses in response to IL-6 and LIF. In contrast, fibroblasts derived from JAK2 null mice can respond to IL-6, with demonstratable tyrosine phosphorylation of gp130, JAK1 and TYK2. Thus it seems JAK1 is the critical JAK required for gp130 signalling. Activation of the same Jaks by all three receptor combinations (gp130/gp130, gp130/LIFR, gp130/OSMR) raises the question of how IL6, LIF and OSM can activate distinct intracellular signaling pathways. Selection of particular substrates, i.e. STAT isoform, depended not on which Jak is activated, but instead are determined by specific motifs, especially tyrosine-based motifs, within each receptor intracellular domain.
IL-31 is a cytokine with an anti-parallel four-helix bundle structure in the gp130/IL-6 cytokine family. This family includes IL-6, IL-11, IL-27, leukemia inhibitory factor (LIF), oncostatin M (OSM), ciliary neurotrophic factor (CNTF), cordiotrophin-1 (CT-1), cardiotrophin-like cytokine (CLC), and neuropoietin (NP). The anti-parallel bundles that these proteins form have an "up-up-down-down" topology, which is a relevant structure regarding the cytokine binding to their respective receptor complex. The cytokines in the IL-6 family signal through type I cytokine receptors. Type I cytokine receptors are defined by sharing their cytokine binding domain (CBD) with conserved cysteine residues and a conserved WSxWS motif in the extracellular domain. The receptors form heteromeric complexes that usually contain the glycoprotein 130 (gp130), which is important for activating downstream signaling pathways. IL-31 is unique in this family of cytokines because its receptor complex does not contain gp130. The receptor for IL-31 is a heterodimer of the interleukin 31 receptor alpha (IL-31RA) and OSMR. IL-31RA was originally referred to as GLM-R (for gp130-like monocyte receptor) or GPL (for gp130-like receptor). Although the IL-31 receptor complex lacks gp130, IL-31RA has similarities to gp130 like its previous descriptors suggest.