0000000000776927

AUTHOR

Christoph Renné

showing 3 related works from this author

Receptor Recognition Sites of Cytokines Are Organized as Exchangeable Modules

1999

Interleukin-6 (IL-6) and ciliary neurotrophic factor (CNTF) are "4-helical bundle" cytokines of the IL-6 type family of neuropoietic and hematopoietic cytokines. IL-6 signals by induction of a gp130 homodimer (e.g. IL-6), whereas CNTF and leukemia inhibitory factor (LIF) signal via a heterodimer of gp130 and LIF receptor (LIFR). Despite binding to the same receptor component (gp130) and a similar protein structure, IL-6 and CNTF share only 6% sequence identity. Using molecular modeling we defined a putative LIFR binding epitope on CNTF that consists of three distinct regions (C-terminal A-helix/N-terminal AB loop, BC loop, C-terminal CD-loop/N-terminal D-helix). A corresponding gp130-bindin…

medicine.medical_specialtybiologyLeukemia inhibitory factor receptorCell BiologyCiliary neurotrophic factorGlycoprotein 130BiochemistryEpitopeCell biologyEndocrinologyInternal medicineLeukemia inhibitory factor receptor bindingmedicinebiology.proteinLeukemia Inhibitory Factor Receptor alpha SubunitBinding siteMolecular BiologyLeukemia inhibitory factorJournal of Biological Chemistry
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Immunoadhesins of interleukin-6 and the IL-6/soluble IL-6R fusion protein hyper-IL-6.

1999

Signal transduction in response to interleukin-6 (IL-6) results from homodimerization of gp130. This dimerization occurs after binding of IL-6 to its surface receptor (IL-6R) and can also be triggered by the complex of soluble IL-6R and IL-6. We fused IL-6 to the constant region of a human IgG1 heavy chain (Fc). IL-6Fc was expressed in COS-7 cells and purified via Protein A Sepharose. Using three different assays we found that the biological activity of this dimeric IL-6 protein is comparable with monomeric IL-6. Recently, we described the designer cytokine Hyper-IL-6 (H-IL-6) in which soluble IL-6R and IL-6 are connected via a flexible peptide linker. This molecule turned out to be 100-100…

Carcinoma HepatocellularRecombinant Fusion ProteinsImmunologyBiologyProtein EngineeringMiceTumor Cells CulturedImmunology and AllergyAnimalsHumansReceptorCOS cellsInterleukin-6HydrolysisThrombinBiological activityProtein engineeringGlycoprotein 130Fusion proteinReceptors Interleukin-6In vitroImmunoglobulin Fc FragmentsBiochemistryImmunoglobulin GCOS CellsSignal transductionImmunoglobulin Heavy ChainsDimerizationJournal of immunological methods
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A New Type of Cytokine Receptor Antagonist Directly Targeting gp130

1998

The interleukin-6-type family of cytokines bind to receptor complexes that share gp130 as a common signal-transducing subunit. So far, receptor antagonists for interleukin-6-type cytokines have been constructed that still bind to the specific ligand binding subunit of the receptor complex, but have lost the ability to stimulate gp130. Such receptor antagonists compete for a specific receptor of a member of the cytokine family. Interleukin-6 only binds to gp130 when complexed with the interleukin-6 receptor that exists as a membrane bound and soluble molecule. Here we have constructed fusion proteins that consist of the soluble form of the human interleukin-6 receptor covalently linked to in…

Receptor complexRecombinant Fusion ProteinsNerve Tissue ProteinsOncostatin MBiologyLeukemia Inhibitory FactorBiochemistryAntigens CDCytokine Receptor gp130Enzyme-linked receptorHumansPoint Mutation5-HT5A receptorCiliary Neurotrophic FactorMolecular BiologyProtease-activated receptor 2Common gamma chainLymphokinesMembrane GlycoproteinsDose-Response Relationship DrugJanus kinase 1Interleukin-6digestive oral and skin physiologyCell BiologyReceptors Interleukin-6Growth Inhibitorsbiological factorsBiochemistryInterleukin-21 receptorCytokinesPeptidesCytokine receptorProtein BindingJournal of Biological Chemistry
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