The functional receptor complex of ciliary neurotrophic factor (CNTF), a member of the gp130 family of cytokines, is composed of CNTF, the CNTF receptor alpha (CNTFR), gp130, and the leukemia inhibitory factor receptor (LIFR). However, the nature of the receptor-mediated interactions in this complex has not yet been resolved. To address this issue we have determined the solution structure of th...

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 in...

Inflammatory cytokines that act through glycoprotein (gp)130 are elevated in the heart after myocardial infarction and in heart failure. These cytokines are potent regulators of neurotransmitter and neuropeptide production in sympathetic neurons but are also important for the survival of cardiac myocytes after damage to the heart. To examine the effect of gp130 cytokines on cardiac nerves, we u...

Toxoplasma gondii infects astrocytes, neurons and microglia cells in the CNS and, after acute encephalitis, persists within neurons. Robust astrocyte activation is a hallmark of Toxoplasma encephalitis (TE); however, the in vivo function of astrocytes is largely unknown. To study their role in TE we generated C57BL/6 GFAP-Cre gp130(fl/fl) mice (where GFAP is glial fibrillary acid protein), whic...

Results The level of cell surface gp130 expression on SF monocytes was reduced compared to peripheral blood (PB) monocytes from patients with JIA. This reduction could be reproduced by stimulating PB monocytes from healthy donors with SF and was dependent on p38 MAPK. The induction of p38 by IL-1b in PB monocytes interfered with IL-6 signaling due to the reduced cell surface expression of gp130...

The pleiotrophic but overlapping functions of the cytokine family that includes interleukin (IL)-6, IL-11, leukemia inhibitory factor, oncostatin M, ciliary neurotrophic factor, and cardiotrophin 1 are mediated by the cytokine receptor subunit gp130 as the common signal transducer. Although mice lacking individual members of this family display only mild phenotypes, animals lacking gp130 are no...

Cytokines of the interleukin-6 family utilize the shared cytokine receptor gp130 in the formation of active signalling complexes. Tyrosine-757 (Y757) on this receptor is critical for negative regulation of gp130-mediated signalling. Two signalling regulators, suppressor of cytokine signalling 3 (SOCS3) and Src homology 2 domain-containing tyrosine phosphatase-2 (SHP2), are recruited to Y757 fol...

The helical cytokine interleukin-6 (IL-6) assembles a multiprotein receptor complex. The starting event in the activation of intracellular signaling is the binding of the IL-6/IL-6R alpha subcomplex to two gp130 chains. The homodimerization of gp130 is triggered by two distinct and independent regions of IL-6 called sites 2 and 3. Several IL-6 antagonists have been obtained that affect signalin...

The interaction of glycoprotein 130 (gp130) with the cytokines of Interleukin-6 (IL-6) family has proved to play a crucial part in several cancers. Our current study is designed to discover the clinical prognostic significance of gp130 in non-metastatic gastric cancer. We examined intratumoral gp130 expression in retrospectively enrolled 370 gastric cancer patients who underwent radical gastrec...

Naturally ligand independent constitutively active gp130 variants were described to be responsible for inflammatory hepatocellular adenomas. Recently, we genetically engineered a ligand-independent constitutively active gp130 variant based on homodimerization of Jun leucine zippers. Because also heterodimeric complexes within the gp130 family may have tumorigenic potential, we seek to generate ...