IndraLab
Statements
reach
"This was the case for the B-K5 antibody, which antagonized the binding of OSM to gp130 but did not interfere with the signals provided by the related cytokines triggering the proliferation of the TF1 erythroleukemia cell line or the induction of haptoglobin synthesis in the HepG2 hepatoma cell line."
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"It has been shown that ESCs maintain their pluripotency when either the LIF or OSM is bound to the gp130 receptor subunit, essentially demonstrating that the LIF plays a massive role in determining whether ESCs differentiate into more specialized cells or they retain their pluripotency for a longer period of time [2]."
sparser
"Researchers at the Universite de Poiters have also developed a patent (WO2020127884A1) relating to specific binding proteins, such as an antibody, that binds specifically to OSM to inhibit interaction with OSM and gp130, and/or LIFR, to be used with any disease associated with elevated levels of OSM, with a particular interest in inflammatory skin diseases and cancer ( xref )."
reach
"OSM can form a
complex with either LIFR/gp130 or OSMR/gp130 , and therefore the effects of OSM and activation of
downstream signaling pathways such as STAT3, ERK, AKT, and Src signaling in breast
cancer cells may be mediated through either LIFR or OSMR, but previous studies have
not determined which receptor is responsible."
sparser
"To transduce its signals in human, OSM binds gp130 with low affinity and as such has little to no biological activity unless a second receptor chain is recruited, either the leukemia inhibitor factor (LIF) receptor α (LIFR α ) or the specific OSM receptor β chain (OSMR β ) (Gearing et al. xref ; Mosley et al. xref ; Tanaka and Miyajima xref )."
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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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"These further illustrate the functional relationship between inflammation/infection, bone, and hematopoietic homeostasis.Although all IL-6 family members use the common receptor subunit glycoprotein 130 (GP130), OSM does this in an unusual way by binding to GP130 before recruiting a second receptor subunit to form its signaling complex (Fig. 2) [38]."
sparser
"This was the case for the B-K5 antibody, which antagonized the binding of OSM to gp130 but did not interfere with the signals provided by the related cytokines triggering the proliferation of the TF1 erythroleukemia cell line or the induction of haptoglobin synthesis in the HepG2 hepatoma cell line."
reach
"Rather few cell types express a cell membrane-bound IL-6R and, in most cases, cells are stimulated by so called trans-signaling in which the hexameric complex is made up by IL-6 initially binding to a soluble IL-6R.Antibodies neutralizing gp130 inhibit the bone resorptive response to IL-6/soluble IL-6R in neonatal mouse calvarial bones, but do not affect the bone resorptive response to OSM, which might be related to the fact that OSM binds to a monomeric gp130, whereas IL-6/soluble IL-6R binds to a homodimer of gp130 [58]."
sparser
"For instance, oncostatin M used during day 16 to 21 of differentiation can bind to heterodimeric cell surface receptors- gp130 and either leukemia inhibiting factor receptor (LIFR) or OSM receptor-beta (OSMR-beta) resulting in activation of JAK-STAT, MAPK, and PI3K/AKT pathways ( xref ; xref ; xref ; xref )."
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"While the previous ones were designed to specifically interact with Site II of OSM (
Figure 2
), this is designed to inhibit OSM/gp130 interaction without directly binding to any amino acids within Site II. Instead, it is designed to interact with amino acids; Pro82, Ser83, Glu84, Leu90, Gly94, Pro112, Gln115, Asp122, Leu123, and Cys152 of OSM."
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"The composite site 3 mediates binding of IL-6 to gp130, of LIF to LIFR and of OSM to LIFR or OSMR (13, 18) and consists of amino acid residues of the C-terminal α-helix and the N-terminal loop connecting helices A and B for site 3-1, the BC loop for site 3-2 and the C-terminal loop connecting helices C and D plus the N-terminal part of helix D for site 3-3 (11, 12)."
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"OSM initially binds with low affinity to the alpha subunit gp130 and then heterodimerizes with high affinity with either the leukemia inhibitory factor receptor (LIFR) β subunit (gp130α/LIFRβ), forming the type 1 complex (OSMR type I), or the OSM receptor β subunit (gp130α/OSMRβ), forming the type II complex (OSMR type II) [13]."
sparser
"Apart from IL‐31, all other IL‐6‐type cytokines induce signal transduction via homodimers of gp130 plus α‐receptor chains for IL‐6, IL‐11 (IL‐6Rα or IL‐11Rα, respectively), or heterodimers of gp130:LIF receptor (LIFR) for CLC, CT‐1, CNTF, LIF and OSM, gp130:OSM‐receptor (OSMR), and gp130:IL‐27 receptor (IL‐27R) for IL‐27 [ xref , xref ]."
sparser
"A Osm–Il6st interaction was predicted to be mediated by Ccr2 − recMacs, Ccr2 + recMacs, Cd163 + Macs, Cx3cr1 hi Macs, MHCII + Macs and cLMTR1, NP, PEP1 and PEP2 neurons at T max,Zy (Extended Data Fig. xref ), but not by Cx3cr1 hi Macs at T max,In and at T max,UV (Extended Data Fig. xref )."
sparser
"In contrast, OSM binds gp130 with low affinity as described by Liu et al. [ xref ] and Gearing et al. [ xref ] and as such has little to no biological activity unless a second receptor chain is recruited, either the LIFR α [ xref ] or the specific OSMReceptor-beta chain (OSMR β ) [ xref ]."
sparser
"While most IL-6 family cytokine–gp130 interactions are of low affinity in the absence of binding to their specific α-receptor (eg, IL-6R, LIFR), OSM binds first to gp130 as a low-affinity α-receptor and then to its specific receptor β OSMR. xref In addition, OSM is the only cytokine in the family that can engage two β-receptors in humans (ie, OSMR and LIFR), being the gp130/OSMR complex the main mediator of most OSM effects. xref Interestingly, the OSMR β-receptor can bind to the specific IL-31 α-receptor to form the IL-31 receptor complex. xref Despite the complexity of OSM signaling and the functional redundancy of some IL-6 family cytokines, OSM-gp130/OSMRβ complex has been shown to activate specific signaling pathways providing evidence that OSM serves unique physiological and pathological functions. xref Unlike gp130, OSMR efficiently induces tyrosine phosphorylation of the Shc isoforms p52 and p66 and their association with Grb2, allowing OSM to drive more potent ERK/MAPK pathway activation than IL-6 or LIF. xref Moreover, OSMR can also induce STAT5a, STAT5b, Akt, c-Jun N-terminal kinase (JNK), p38, and PKCd activation in a context-dependent manner. xref "
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"To transduce its signals in human, OSM binds gp130 with low affinity and as such has little to no biological activity unless a second receptor chain is recruited, either the leukemia inhibitor factor (LIF) receptor alpha (LIFRalpha) or the specific OSM receptor beta chain (OSMRbeta)."
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"In contrast, OSM binds gp130 with low affinity as described by Liu et al. [XREF_BIBR] and Gearing et al. [XREF_BIBR] and as such has little to no biological activity unless a second receptor chain is recruited, either the LIFRalpha [XREF_BIBR] or the specific OSMReceptor-beta chain (OSMRbeta) [XREF_BIBR]."