EurekaMag
+ Translate
+ Most Popular
Advantages and disadvantages of bordeaux mixture and of lime-sulphur used on apples in the growing season
Observations on the Umaria marine bed
10 years of hearing conservation in the Royal Air Force
Chocolate crumb - dairy ingredient for milk chocolate
Effect of daily gelatin ingestion on human scalp hair
Comparison of rice bran and maize bran as feeds for growing and fattening pigs
The composition of pampas-grass (Cortaderia argentea.)
The Accraian Series:
The mechanism of the Liebermann-Burchard reaction of sterols and triterpenes and their esters
Cerebrovascular Doppler ultrasound studies (cv-Doppler)
Toria: PT-303 - first national variety
Hair growth promoting activity of tridax procumbens
Productivity of Pekin x Khaki Campbell ducks
A stable cytosolic expression of VH antibody fragment directed against PVY NIa protein in transgenic potato plant confers partial protection against the virus
Solar treatment of wheat loose smut
Swimmers itch in the Lake of Garda
Bactofugation and the Bactotherm process
The effects of prefrontal lobotomy on aggressive behavior in dogs
Visual rating scales for screening whorl-stage corn for resistance to fall armyworm
Breakdown of seamounts at the trench axis, viewed from gravity anomaly
Kooken; pennsylvania's toughest cave
Recovery of new dinosaur and other fossils from the Early Cretaceous Arundel Clay facies (Potomac Group) of central Maryland, U.S.A
Zubor horny (Bison bonasus) v prirodnych podmienkach Slovensku
The extended Widal test in the diagnosis of fevers due to Salmonella infection
Hair of the american mastodon indicates an adaptation to a semi aquatic habitat

Signal transduction of IL-6, leukemia-inhibitory factor, and oncostatin M: structural receptor requirements for signal attenuation


Signal transduction of IL-6, leukemia-inhibitory factor, and oncostatin M: structural receptor requirements for signal attenuation



Journal of Immunology 165(5): 2535-2543



ISSN/ISBN: 0022-1767

PMID: 10946280

DOI: 10.4049/jimmunol.165.5.2535

Stimulation of the IL-6R complex leads to Src homology domain containing tyrosine phosphatase 2 (SHP2) recruitment to the receptor subunit gp130 and its subsequent tyrosine phosphorylation. SHP2 is a two-SH2 domain-containing protein tyrosine phosphatase that is activated by many cytokines and growth factors. SHP2 counteracts the activation of transcription factors of the STAT family and the induction of IL-6-responsive genes. Tyrosine 759 of gp130, the signal transducing subunit of the IL-6R complex, is essential for the phosphorylation of SHP2. Mutation of tyrosine 759 to phenylalanine leads to an enhanced inducibility of IL-6-dependent genes. Here we demonstrate that no further tyrosines in the cytoplasmic part of gp130 are required for the phosphorylation of SHP2. We also tested whether the tyrosine 759 motifs in both subunits of the gp130 dimer are required for SHP2 association and tyrosine phosphorylation. Interestingly, one SHP2-recruiting phosphotyrosine motif in a single chain of the gp130 dimer is sufficient to mediate SHP2 association to the gp130 receptor subunit and its tyrosine phosphorylation as well as to attenuate IL-6-dependent gene induction. Furthermore, we show that repression of gene induction via Y759 does not require the presence of the SHP2 and STAT recruitment sites within the same receptor subunit, but within the same receptor complex. The Y759 motif in gp130 also attenuates gene induction mediated by the oncostatin M and leukemia inhibitory factor receptor complexes, which both contain gp130 as the shared subunit.

Please choose payment method:






(PDF emailed within 0-6 h: $19.90)

Accession: 018115411

Download citation: RISBibTeXText

Related references

Contributions of leukemia inhibitory factor receptor and oncostatin M receptor to signal transduction in heterodimeric complexes with glycoprotein 130. Journal of Immunology 163(12): 6651-6658, 1999

Differential induction of signal transduction pathways by oncostatin M and leukemia inhibitory factor in human glioma cell lines. Society for Neuroscience Abstracts 23(1-2): 2446, 1997

Murine Oncostatin M Acts via Leukemia Inhibitory Factor Receptor to Phosphorylate Signal Transducer and Activator of Transcription 3 (STAT3) but Not STAT1, an Effect That Protects Bone Mass. Journal of Biological Chemistry 291(41): 21703-21716, 2016

Mannose 6-Phosphate/Insulin-like growth factor II receptor mediates internalization and degradation of leukemia inhibitory factor but not signal transduction. Journal of Biological Chemistry 274(35): 24685-24693, 1999

Distinct roles for leukemia inhibitory factor receptor a-chain and gp130 in cell type-specific signal transduction. The Journal of Biological Chemistry 272: 982-6, 1997

Distinct roles for leukemia inhibitory factor receptor alpha-chain and gp130 in cell type-specific signal transduction. Journal of Biological Chemistry 272(32): 19982-19986, 1997

Activation of signal transducers and activator of transcription 1 and 3 by leukemia inhibitory factor, oncostatin-M, and interferon-c in adipocytes. The Journal of Biological Chemistry 273(47): 408-16, 1998

Multiple regions within the cytoplasmic domains of the leukemia inhibitory factor receptor and gp130 cooperate in signal transduction in hepatic and neuronal cells. Molecular and Cellular Biology 14(1): 138-146, 1994

Activation of signal transducers and activators of transcription 1 and 3 by leukemia inhibitory factor, oncostatin-M, and interferon-gamma in adipocytes. Journal of Biological Chemistry 273(47): 31408-31416, 1998

Increased expression of epidermal growth factor receptor induces sequestration of extracellular signal-related kinases and selective attenuation of specific epidermal growth factor-mediated signal transduction pathways. Molecular Cancer Research: Mcr 1(3): 219-233, 2003

Oncostatin M, leukemia inhibitory factor, and interleukin 6 induce the proliferation of human plasmacytoma cells via the common signal transducer, gp130. Journal of Experimental Medicine 179(4): 1343-1347, 1994

Structural requirements for signal transduction of the insulin receptor. European Journal of Biochemistry 191(2): 473-482, 1990

Oncostatin M and leukaemia inhibitory factor trigger signal transducer and activator of transcription 3 and extracellular signal-regulated kinase 1/2 pathways but result in heterogeneous cellular responses in trophoblast cells. Reproduction Fertility and Development 28(5): 608-617, 2016

Ciliary neurotropic factor, interleukin 11, leukemia inhibitory factor, and oncostatin M are growth factors for human myeloma cell lines using the interleukin 6 signal transducer gp130. Journal of Experimental Medicine 179(4): 1337-1342, 1994

A unique loop structure in oncostatin M determines binding affinity toward oncostatin M receptor and leukemia inhibitory factor receptor. Journal of Biological Chemistry 287(39): 32848-32859, 2012