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OSM activates IL6ST. 43 / 49
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"Furthermore, we showed that the small molecule gp130 inhibitor SC144 suppresses the PDAC cell viability and proliferation and inhibits IL-6 and OSM-induced gp130/STAT3 signaling in vitro.Our previous study on tissue micro-arrays from a cohort of 175 patients with PDAC showed that STAT3, phosphorylated STAT3, and IL-6 were expressed in more than half of the examined pancreatic tumors, supporting the importance of this pathway in pancreatic cancer (Pozios et al. 2018)."
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"3-5 OSM can also elicit an active heterodimer of gp130 and the OSM receptor (OSMR)."
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"Since the IL-6 family is thought to have the highest degree of functional pleiotropy and redundancy in triggering the health- and disease-related responses of all cytokine families [27], the unique effects of OSM-activated gp130 receptor complexes feature less in the scientific focus of heart diseases."
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"However, only OSM activates the OSM receptor (OSMR) and gp130 complex."
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"LIFR and gp130 can be activated by either LIF or OSM, but OSMR and gp130 is activated only by OSM [18]."
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"Gp130 and OSMR is activated only by OSM, but gp130 and LIFR can be activated by either LIF, OSM or both."
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"50 The observation that LIF and OSM induce a complex of gp130 and RILLIFDeltaII that is as active as the wild-type LIFR complex negates the hypothesis that this CBM is an important dimerization site i[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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"It has been reported that IL-6 type cytokines such as IL-6 or OSM enhance GP130 promotor activity via activated STATs in HepG2 hepatoma cells and that LIF upregulates STAT3 in mouse embryonic stem cel[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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"Apart from IL-6, other gp130 activators such as LIF, OSM and CNTF can also induce astrogliosis (Damiani and O'Callaghan, 2007; Sriram et al., 2004)."
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"Promotion of cardiomyocyte proliferation by macrophages occurs through secretion of OSM, which activates gp130 and subsequently triggers Yap activation via Src during heart regeneration [15] ."
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"Additionally, OSM induced biological effects by activating functional receptor complexes of the common signal transducing component gp130 and OSMRβ or LIFR, which are mainly involved in chronic inflammatory and cardiovascular diseases, cancer and rheumatoid arthritis ."
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"Similarly, human OSM only activates gp130 and OSMRbeta and not LIFR in human adipocytes."
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"LIFR:gp130-expressing cells proliferated with LIF, and OSM, while OSM also induced the proliferation of OSMR:gp130-expressing cells."
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"Notably, contributions of other gp130-dependent IL-6 family cytokines (OSM, LIF, IL-11) in regulating L-selectin adhesion were only revealed in IL-6 −/− mice where immune systems develop without IL-6."
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"Similarly, human OSM only activates gp130 and OSMRβ and not LIFR in human adipocytes."
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"Oncostatin M. Oncostatin M (OSM) is an inflammatory cytokine that also belongs to the family of gp130 related cytokines, and as such, OSM stimulates transmembrane signaling by binding and activating either of two receptor complexes : (1) gp130 and LIFR (leukemia inhibitor factor receptor) heterodimers, and (2) gp130 and OSM receptor (OSMR)."
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"In this study we have clearly demonstrated that OSM induction of IL-6, RANKL, OSMR, gp130 and IL-1R1 in mouse SFs requires expression of its ligand specific receptor, OSMR."
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"53 As a member of the IL-6 family of cytokines, OSM has homogenous protein sequence and structure as that of other family members.57 Studies in the mouse showed that human OSM activates the heterodimer of LIF receptor B and gp130, as does CNTF.58 59 An increase in STAT3 phosphorylation was localized to Müller cells after intravitreal delivery of OSM in an ONC model, indicating that the neuroprotective effect of OSM on the RGC is medicated by Müller cells."
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"Our recent research reported that OSM-mediated signaling activation through OSMR dimerization with IL6ST is important for Signaling Transducer and Activator of Transcription 3 (STAT3), which is known for oncogenic transformation and blocks apoptosis in both breast and ovarian cancers ."
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"The drug 423F is a gp130 modulator that acts via promoting gp130 homodimerization and preventing IL-6 and Oncostatin M-induced heterodimerization with IL-6R and OSMR respectively."
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"Previous studies have reported that OSM treatment increases gp130 promoter activities and enhances the synthesis of OSMRbeta and gp130, and to a lesser extent, LIFR in various cell lines [40]."
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"Promotion of cardiomyocyte proliferation by macrophages occurs through secretion of OSM, which activates gp130 and subsequently triggers Yap activation via Src during heart regeneration [15] ."
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"IL-6 and IL-11 initiate signaling via homodimerization of gp130, while LIF and OSM initiates signaling by heterodimerizing gp130 along with LIFR (67)."
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"OSM also activates gp130, either via its own OSM receptor (OSMRβ) subunit or via LIFR ( xref )."
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"Mechanistically, OSM activates the heterodimeric receptor complex gp130:OSMR [ xref ], resulting in the activation of JAK/STAT [ xref ] and MAPK signaling pathways."
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"To investigate whether B14 and B21 monoclonal antibodies (mAbs) inhibit OSM-induced dimerization of OSMR with IL6ST, we immunoprecipitated OSMR-IL6ST heterodimer complex cross-linked after treating with anti-OSMR antibody or control IgG."
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"Using a dominant negative LIF mutant (hLIF-05), we showed that in RC cell cultures mouse OSM (mOSM) activates exclusively glycoprotein 130 (gp130)/OSMR."
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"A previous study indicated that OSM stimulation increases gp130 promoter activity [41] ."
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"The duration of Stat3 tyrosine phosphorylation that was induced by OSM was longer than that caused by other IL-6 family cytokines in the gp130 WT/WT osteoblasts, and the prolonged activation induced b[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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"OSM activates a complex of OSM receptor (OSMR) and IL6ST."
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"On the molecular level this usage of OSM from different species results in the stimulation of different receptor complexes : human OSM exclusively binds to the type I gp130 and LIFR system in mouse cells; murine OSM, however, exclusively activates the type II gp130 and OSMR system."
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"LIF can be substituted by Oncostatin-M and IL-6 (in combination with soluble IL-6 receptor), both of which activate the gp130 receptor (Koshimizu et al., 1996)."
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"Gp130 and LIFR can be activated by LIF or OSM, but gp130 and OSMR is activated by OSM only."
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"Since the IL-6 family is thought to have the highest degree of functional pleiotropy and redundancy in triggering the health- and disease-related responses of all cytokine families [ xref ], the unique effects of OSM-activated gp130 receptor complexes feature less in the scientific focus of heart diseases."
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"OSM signals through a heterodimer of gp130 and the OSM receptor."
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"Studies on the mechanisms involved suggest that Toll-like receptor activation induces monocyte production of Oncostatin M (OSM) through induction of COX-2 and prostaglandin E2 (PGE ) and is responsible for bone formation through OSM signaling of gp130 on MSCs."
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"Importantly, OSM induces the dimerization of OSMR with another receptor partner IL6ST."
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"OSM can induce the formation of a dimer of gp130 with LIFR or the related protein, oncostatin M receptor."
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"Using a dominant-negative LIF mutant (hLIF-05), we showed that in RC cell cultures mouse OSM (mOSM) activates exclusively glycoprotein 130 (gp130)/OSMR."
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"The transcriptional induction of gp130 by OSM in ovarian carcinoma cell lines overexpressing LIFRβ/OSMRβ could maintain STAT3 in its phosphorylated and activated form, which was correlated with the ma[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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"In the AGM culture system, supplementation of OSM, which activates gp130, has been shown to be indispensable in addition to bFGF and SCF [12] ."
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"Mechanistically, OSM activates the heterodimeric receptor complex gp130:OSMR [7], resulting in the activation of JAK/STAT [8] and MAPK signaling pathways."
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"In this study using several gp130 mutants, we investigated requirements for gp130 activation by the cytokines LIF and OSM."
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