gp130 dimerization in the absence of ligand: Preformed cytokine receptor complexes

Tenhumberg, Stephanie; Schuster, Björn; Zhu, Lixin; Kovaleva, Marina; Scheller, Jürgen; Kallen, Karl-Josef; Rose-John, Stefan

doi:10.1016/j.bbrc.2006.05.173

Cited by 53 publications

(42 citation statements)

References 42 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…There are reports that gp130 can exist as preformed inactive homodimers or as heterodimers with LIFR in the absence of ligand (34,35). In the case of the erythropoietin receptor (EpoR), ligand-independent oligomerization is mediated by the transmembrane domain (36), and it is possible that any direct interaction between gp130 molecules also occurs in this region.…”

Section: Discussionmentioning

confidence: 99%

Crystal Structure of the Entire Ectodomain of gp130

Kershaw

Luo

et al. 2010

Journal of Biological Chemistry

View full text Add to dashboard Cite

gp130 is the shared signal-transducing receptor subunit for the large and important family of interleukin 6-like cytokines. Previous x-ray structures of ligand-receptor complexes of this family lack the three membrane-proximal domains that are essential for signal transduction. Here we report the crystal structure of the entire extracellular portion of human gp130 (domains 1-6, D1-D6) at 3.6 Å resolution, in an unliganded form, as well as a higher resolution structure of the membraneproximal fibronectin type III domains (D4 -D6) at 1.9 Å . This represents the first atomic resolution structure of the complete ectodomain of any "tall" cytokine receptor. These structures show that other than a reorientation of the D1 domain, there is little structural change in gp130 upon ligand binding. They also reveal that the interface between the D4 and D5 domains forms an acute bend in the gp130 structure. Key residues at this interface are highly conserved across the entire tall receptor family, suggesting that this acute bend may be a common feature of these receptors. Importantly, this geometry positions the C termini of the membrane-proximal fibronectin type III domains of the tall cytokine receptors in close proximity within the transmembrane complex, favorable for receptor-associated Janus kinases to trans-phosphorylate and activate each other.

show abstract

Section: Discussionmentioning

confidence: 99%

Crystal Structure of the Entire Ectodomain of gp130

Kershaw

Luo

et al. 2010

Journal of Biological Chemistry

View full text Add to dashboard Cite

show abstract

“…In sgp130Fc, the complete extracellular part of gp130 (domains D1-D6) was fused to a dimerization domain (Fc part of a human IgG antibody). Therefore, sgp130Fc mimics the receptor signaling complex on the cell membrane, which also exists as a preformed dimer (25). Interestingly, the preformed sgp130Fc dimer has a 10 -100-fold higher efficacy in inhibiting IL-6/sIL-6R-mediated responses than the naturally occurring monomeric sgp130 isoform (1).…”

Section: Discussionmentioning

confidence: 99%

Alternative Intronic Polyadenylation Generates the Interleukin-6 Trans-signaling Inhibitor sgp130-E10

Sommer

Garbers²,

Wolf³

et al. 2014

Journal of Biological Chemistry

Self Cite

View full text Add to dashboard Cite

Background: Interleukin (IL)-6 trans-signaling is inhibited by naturally occurring soluble gp130 (sgp130) variants. Results: Alternative intronic polyadenylation in the gp130 gene creates the novel natural IL-6 trans-signaling inhibitor sgp130-E10. Conclusion: Alternative mRNA polyadenylation contributes to regulation of IL-6 trans-signaling intensity. Significance: This is the first report on a soluble isoform of the key cytokine co-receptor gp130 originating from alternative polyadenylation.

show abstract

“…HepG2 cells have been previously shown to express the specific IL-6 receptor. 23 The MeOH extracts of P. longum and P. nigrum were fractionated by repeated open-column chromatography on silica gel and ODS, LPLC and semi-preparative HPLC to afford nine alkamides (1-9), and they showed inhibitory effects on Stat3-dependent luciferase activities induced by IL-6. Compound 7 was isolated as colorless oil, which exhibited a UV spectrum with λmax at 260.5 and 305 nm.…”

Section: Resultsmentioning

confidence: 99%

Alkamides from Piper longum and Piper nigrum as Inhibitors of IL-6 action

Lee¹,

Kim²,

Park³

et al. 2010

Bulletin of the Korean Chemical Society

View full text Add to dashboard Cite

Blocking of IL-6 has been postulated to be an effective therapy in the pathogenesis of several inflammatory diseases. The current study was performed to examine the potential effects of alkamides isolated from P. longum and P. nigrum on IL-6 induced Stat3 activation and identify the structure-activity relationship of these alkamides in human hepatoma cells. Among 10 alkamides isolated from P. longum and P. nigrum, compounds 6, 7 and 9 were identified as strong inhibitors of IL-6 action, which inhibit IL-6 induced Stat3-dependent luciferase activities. These inhibitory activities were positively influenced by the presence of piperidine moiety.

show abstract

gp130 dimerization in the absence of ligand: Preformed cytokine receptor complexes

Cited by 53 publications

References 42 publications

Crystal Structure of the Entire Ectodomain of gp130

Crystal Structure of the Entire Ectodomain of gp130

Alternative Intronic Polyadenylation Generates the Interleukin-6 Trans-signaling Inhibitor sgp130-E10

Alkamides from Piper longum and Piper nigrum as Inhibitors of IL-6 action

Contact Info

Product

Resources

About