CNTF and LIF act on neuronal cells via shared signaling pathways that involve the IL-6 signal transducing receptor component gp130

Ip, Nancy Y.; Nye, Steven H.; Boulton, Teri G.; Davis, Samuel; Taga, Tetsuya; Li, Yanping; Birren, Susan J.; Yasukawa, Kiyoshi; Kishimoto, T.; Anderson, David J.; Stahl, Neil; Yancopouloš, George D.

doi:10.1016/0092-8674(92)90634-o

Cited by 670 publications

(350 citation statements)

References 42 publications

Supporting

Mentioning

340

Contrasting

Unclassified

Order By: Relevance

“…The transmembrane expression of OSMR␤ was studied by labeling the A375 extracellular surface with a water-soluble biotin ester. After activating the cells with OSM we analyzed the gp130-associated protein(s) that were both tyrosine-phosphorylated and biotinylated (21). The obtained results show the presence in the A375 cells of a 150 -180-kDa transmembrane protein very likely corresponding to OSMR␤ (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…For cell surface biotinylation, the A375 cells were starved for a 4 -6-h period before being stimulated with 50 ng/ml OSM for 5 min. Then, the cells were washed with PBS and incubated for 20 additional minutes in PBS, 0.1 M Hepes, pH 8, 0.5 mg/ml water-soluble sulfo-NHSbiotin (Pierce) (21). After the contact period the reaction was stopped by adding 0.1 M Tris/HCl, pH 8.…”

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Signaling of Type II Oncostatin M Receptor

Auguste

Guillet²,

Fourcin

et al. 1997

Journal of Biological Chemistry

105

View full text Add to dashboard Cite

Oncostatin M (OSM) mediates its bioactivities through two different heterodimer receptors. They both involve the gp130-transducing receptor, which dimerizes with either leukemia inhibitory receptor ␤ or with OSM receptor ␤ (OSMR␤) to generate, respectively, type I and type II OSM receptors. Co-precipitation of gp130-associated proteins, flow cytometry, polymerase chain reaction, and tyrosine phosphorylation analyses allowed the characterization of both types of OSM receptors expressed on the surface of different cell lines. It also allowed the detection of a large size protein, p250, that specifically associates to the type II OSM receptor components and that is tyrosine-phosphorylated after the activation peak of the gp130⅐OSMR␤ heterocomplex. The restricted expression of type I OSM receptor by the JAR choriocarcinoma cell line, and type II receptor by the A375 melanoma cell line, permitted the characterization of their signaling machineries. Both type I and type II OSM receptors activated Jak1, Jak2, and Tyk2 receptor-associated tyrosine kinases. The information is next relayed to the nucleus by the STAT3 transcriptional activator, which is recruited by both types of OSM receptors. In addition, STAT5b was specifically activated through the gp130⅐OSMR␤ type II heterocomplex.The signaling pathway differences observed between the common type I LIF/OSM receptor and the specific type II OSM receptor might explain some of the bioactivities specifically displayed by OSM.Oncostatin M (OSM) 1 is a multifunctional cytokine belonging to the interleukin-6 (IL-6) family and that shares many properties with those reported for LIF (1). Both OSM and LIF are able to inhibit the spontaneous differentiation of embryonic stem cells (2). They also induce the terminal differentiation of the M1 murine myeloid cell line (3). Like the other IL-6 family members, OSM has been shown to induce acute phase protein synthesis in hepatocytes (4). Beside these LIF-shared bioactivities, OSM displays some specific properties and can inhibit the growth of a variety of solid tumor cells (5) and triggers in vitro the proliferation of Kaposi's sarcoma-derived cell lines (6, 7). In addition, expression of an oncostatin M transgene in the early T cell lineage stimulates a dramatic accumulation of T cells in the mice lymph nodes (8).The redundancy of OSM and LIF biological properties is in part explained by the shared use of a common heterocomplex receptor composed of the gp130 signal transducing protein associated with the LIF receptor ␤ (LIFR␤) component (9, 10). Binding experiments have pointed out the existence of a second and different high affinity receptor for OSM (also referred to as type II OSM receptor) (9 -11). Type II OSM receptor complex binds OSM in a specific manner and is not recognized by LIF (9 -11). Type II receptor also involves a gp130-transducing component that associates with a second receptor subunit very recently isolated as OSM receptor ␤ (OSMR␤), which displays an apparent molecular mass of 180 kDa (12). Comparison of OSMR␤ t...

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Signaling of Type II Oncostatin M Receptor

Auguste

Guillet²,

Fourcin

et al. 1997

Journal of Biological Chemistry

105

View full text Add to dashboard Cite

show abstract

“…gp130 also forms part of the receptor-complexes of LIF, OSM, CNTF, IL-11 (Gearing et al, 1992;Ip et al, 1992;Liu et al, 1992;Taga et al, 1992;Fourcin et al, 1994), as well as CT-1 (Pennica et al, 1995). Targeted disruption of gp130 in mice is lethal during early embryogenesis due to impaired myocardial development and hematopoiesis (Yoshida et al, 1996), whereas continuous activation of gp130 in mice transgenic for both IL-6 and the ILdR causes myocardial hypertrophy (Hirota et al, 1995).…”

Section: Structure Of the Interleukin-6 Receptor And Gp130mentioning

confidence: 99%

“…Given that a common mechanism of activation of transmembrane receptors involves dimerization of their cytoplasmic domains (reviewed by Ullrich & Schlessinger, 1990;Heldin, 1995), and that the transmembrane and cytoplasmic domains of the IL6R are not necessary for signaling (Taga et al, 1989;Hibi et al, 1990), intracellular signaling induced by IL-6 was postulated to involve gp130 dimerization (Ip et al, 1992). It was later shown that bind-ing of E -6 to the IL-6R induced gp130 homodimerization, which correlated with tyrosine kinase activation (Davis et al, 1993b;Murakami et al, 1993).…”

Section: The Ternary Complexmentioning

confidence: 99%

Interleukin‐6: Structure‐function relationships

et al. 1997

View full text Add to dashboard Cite

Interleukin-6 (IL-6) is a multifunctional cytokine that plays a central role in host defense due to its wide range of immune and hematopoietic activities and its potent ability to induce the acute phase response. Overexpression of IL-6 has been implicated in the pathology of a number of diseases including multiple myeloma, rheumatoid arthritis, Castleman's disease, psoriasis, and post-menopausal osteoporosis. Hence, selective antagonists of IL-6 action may offer therapeutic benefits. IL-6 is a member of the family of cytokines that includes interleukin-1 1, leukemia inhibitory factor, oncostatin M, cardiotrophin-1, and ciliary neurotrophic factor. Like the other members of this family, IL-6 induces growth or differentiation via a receptor-system that involves a specific receptor and the use of a shared signaling subunit, gp130. Identification of the regions of IL-6 that are involved in the interactions with the IL-6 receptor and gp130 is an important first step in the rational manipulation of the effects of this cytokine for therapeutic benefit. In this review, we focus on the sites on IL-6 which interact with its low-affhity specific receptor, the IL-6 receptor, and the high-affinity converter gp130. A tentative model for the IL-6 hexameric receptor ligand complex is presented and discussed with respect to the mechanism of action of the other members of the IL-6 family of cytokines.

show abstract

“…IL-6 initiates its action by binding to its receptor which is composed of two subunits : an 80-kDa IL-6 binding protein and a 130-kDa transmembrane signaltransducing component (gp130) [4][5][6]. The gp130 receptor protein is also used by other members of the IL-6 cytokine family, including IL-11, oncostatin M, leukaemia inhibitory factor, and ciliary neurotrophic factor [7][8][9]. Activation of IL-6 signal transduction involves gp130 dimerization, ligand-dependent tyrosine phosphorylation of the gp130-associated protein-tyrosine kinases Jak1, Jak2 and Tyk2, as well as tyrosine phosphorylation of signal transducer and activator of transcription 3 (STAT3) [10].…”

Section: Introductionmentioning

confidence: 99%

Interleukin-6-induced STAT3 transactivation and Ser727 phosphorylation involves Vav, Rac-1 and the kinase SEK-1/MKK-4 as signal transduction components

Schuringa¹,

Jonk²,

Dokter³

et al. 2000

Biochemical Journal

View full text Add to dashboard Cite

In the present study, signal transducer and activator of transcription 3 (STAT3) Ser(#( phosphorylation and transactivation was investigated in relation to activation of mitogen-activated protein (MAP) kinase family members including extracellularsignal-regulated protein kinase (ERK)-1, c-Jun N-terminal kinase (JNK)-1 and p38 (' reactivating kinase ') in response to interleukin (IL)-6 stimulation. Although IL-6 can activate ERK-1 in HepG2 cells, STAT3 transactivation and Ser(#( phosphorylation were not reduced by using the MAP kinase\ERK kinase (MEK) inhibitor PD98059 or by overexpression of dominant-negative Raf. IL-6 did not activate JNK-1 in HepG2 cells and STAT3 was a poor substrate for JNK-1 activated by anisomycin, excluding a role for JNK1 in IL-6-induced STAT3 activation. However, SEK-1\MKK-4 [where SEK-1 stands for stress-activated protein kinase (SAPK)\ERK kinase 1, and MKK-4 stands for MAP kinase kinase 4] was activated in response to IL-6 and overexpression of dominant-negative SEK-1\MKK-4(A-L) reduced

show abstract

CNTF and LIF act on neuronal cells via shared signaling pathways that involve the IL-6 signal transducing receptor component gp130

Cited by 670 publications

References 42 publications

Signaling of Type II Oncostatin M Receptor

Signaling of Type II Oncostatin M Receptor

Interleukin‐6: Structure‐function relationships

Interleukin-6-induced STAT3 transactivation and Ser727 phosphorylation involves Vav, Rac-1 and the kinase SEK-1/MKK-4 as signal transduction components

Contact Info

Product

Resources

About