Research Topics
Genomes and Genes
| Peter C HeinrichSummaryAffiliation: RWTH Aachen Country: Germany Publications
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Detail Information
Publications
Interleukin-6-type cytokine signalling through the gp130/Jak/STAT pathwayP C Heinrich
Institut fur Biochemie, RWTH Aachen, Universitatsklinikum, Pauwelsstrasse 30, D 52057 Aachen, Germany
Biochem J 334:297-314. 1998..This is reflected in the different phenotypes of IL-6-type-cytokine knock-out animals...- Principles of interleukin (IL)-6-type cytokine signalling and its regulationPeter C Heinrich
Institut fur Biochemie, RWTH Aachen, Universitatsklinikum, Pauwelsstrasse 30, D 52074 Aachen, Germany
Biochem J 374:1-20. 2003..Also the cross-talk between the JAK/STAT pathway with other signalling cascades is discussed... 
Real time analysis of STAT3 nucleocytoplasmic shuttlingAlbert L Pranada
Institut fur Biochemie, Universitätsklinikum Rheinisch Westfälische Technische Hochschule Aachen, Pauwelsstrasse 30, Aachen 52057, Germany
J Biol Chem 279:15114-23. 2004..The new approach presented in this study is generally applicable to any protein of interest for analyzing nucleocytoplasmic transport mechanisms in real time...- Mechanisms of SOCS3 phosphorylation upon interleukin-6 stimulation. Contributions of Src- and receptor-tyrosine kinasesUlrike Sommer
Institut fur Biochemie, Rheinisch Westfälische Technische Hochschule Aachen, Pauwelsstrasse 30, D 52074 Aachen, Germany
J Biol Chem 280:31478-88. 2005.... - Dimerization of the cytokine receptors gp130 and LIFR analysed in single cellsBernd Giese
Institut fur Biochemie, Universitätsklinikum RWTH Aachen, Pauwelsstrasse 30, 52074 Aachen, Germany
J Cell Sci 118:5129-40. 2005..This view is supported by the observation that the simultaneous action of two IL-6 binding domains on two gp130 molecules is required to efficiently recruit a fluorescent IL-6 (YFP-IL-6) to the plasma membrane... - Oncostatin M receptor-mediated signal transduction is negatively regulated by SOCS3 through a receptor tyrosine-independent mechanismClaudia Stross
, , Pauwelsstrasse 30, 52074 Aachen, Germany
J Biol Chem 281:8458-68. 2006..However, the inhibition occurs independent of tyrosine motifs within the OSMR. Instead, SOCS3 interacts directly with JAK1 in a stimulation-dependent manner, a mechanism so far only known for SOCS1... - The role of the inhibitors of interleukin-6 signal transduction SHP2 and SOCS3 for desensitization of interleukin-6 signallingPatrick Fischer
Department of Biochemistry, Faculty of Medicine, RWTH Aachen, Pauwelsstrasse 30, D 52074 Aachen, Germany
Biochem J 378:449-60. 2004..Furthermore, cells lacking SOCS3 show constitutive STAT3 activation which is not affected by pre-stimulation with IL-6. All these observations suggest that desensitization and inhibition of signalling are mechanistically distinct... - Are STATS arginine-methylated?Waraporn Komyod
Institut fur Biochemie, Universitätsklinikum der Rheinisch Westfälischen Technischen Hochschule Aachen, Pauwelsstrasse 30, 52074 Aachen, Germany
J Biol Chem 280:21700-5. 2005..Taken together, our data suggest the absence of arginine methylation of STAT1 and STAT3... - The Jak1 SH2 domain does not fulfill a classical SH2 function in Jak/STAT signaling but plays a structural role for receptor interaction and up-regulation of receptor surface expressionSimone Radtke
Institut fur Biochemie, Uniklinik Aachen, Pauwelsstrasse 30, 52074 Aachen, Germany
J Biol Chem 280:25760-8. 2005..Likewise, the signaling capacity of Jak1 was not affected by this point mutation. However, we found that the SH2 domain is structurally important for cytokine receptor binding and surface expression of the OSMR... - STAT3 is enriched in nuclear bodiesAndreas Herrmann
Institut fur Biochemie, Universitätsklinikum RWTH Aachen, Pauwelsstrasse 30, 52057 Aachen, Germany
J Cell Sci 117:339-49. 2004..Taken together, our data suggest that STAT3 nuclear bodies are either directly involved in active gene transcription or they serve as reservoirs of activated STAT3... - Dual function of interleukin-1beta for the regulation of interleukin-6-induced suppressor of cytokine signaling 3 expressionXiang Ping Yang
Department of Biochemistry, Medical School, Rheinisch Westfälische Technische Hochschule Aachen, Pauwelsstrasse 30, D 52074 Aachen, Germany
J Biol Chem 279:45279-89. 2004.... - The tyrosine 974 within the LIF-R-chain of the gp130/LIF-R heteromeric receptor complex mediates negative regulation of LIF signallingThomas Clahsen
Department of Biochemistry, Medical School RWTH Aachen, Pauwelsstrasse 30, D-52074 Aachen, Germany
Cell Signal 17:559-69. 2005..This observation was further corroborated by experiments indicating that mainly gp130 contributes to the inhibition of signalling by SOCS3... - Nucleocytoplasmic shuttling of persistently activated STAT3Andreas Herrmann
Institut fur Biochemie, Universitätsklinikum RWTH Aachen, Pauwelsstrasse 30, 52074 Aachen, Germany
J Cell Sci 120:3249-61. 2007..We propose passage of persistently activated STAT3 through the nuclear pore complex as a new target for intervention in cancer... - Characterization of the Interleukin (IL)-6 Inhibitor IL-6-RFP: fused receptor domains act as high affinity cytokine-binding proteinsSilke Metz
Institut fur Biochemie, Pauwelsstrasse 30, Universitätsklinikum RWTH Aachen, Germany
J Biol Chem 282:1238-48. 2007..Thus, fusion of the ligand binding domains of heteromeric receptors leads to highly specific cytokine inhibitors with superior activity compared with the separate soluble receptors... - Janus kinase (Jak) subcellular localization revisited: the exclusive membrane localization of endogenous Janus kinase 1 by cytokine receptor interaction uncovers the Jak.receptor complex to be equivalent to a receptor tyrosine kinaseIris Behrmann
Institut fur Biochemie, Universitatsklinikum Aachen, Pauwelsstrasse 30, 52074 Aachen, Germany
J Biol Chem 279:35486-93. 2004..Finally we show that Jak1 remains a membrane-localized protein after cytokine stimulation. These data strongly support the hypothesis that cytokine receptor.Janus kinase complexes can be regarded as receptor tyrosine kinases... - Long term association of the cytokine receptor gp130 and the Janus kinase Jak1 revealed by FRAP analysisBernd Giese
, , Pauwelsstrasse 30, 52057 Aachen, Germany
J Biol Chem 278:39205-13. 2003..We conclude from these findings that Jak1, once bound to a gp130 molecule, does not exchange between different receptors at the plasma membrane neither via the cytoplasmic compartment nor via a membrane-associated state... - Multiple reasons for an inefficient STAT1 response upon IL-6-type cytokine stimulationSerge Haan
, , Pauwelsstrasse 30, 52074 Aachen, Germany
Cell Signal 17:1542-50. 2005..We also describe that pY-STAT3 is much more efficiently shuttled into the nucleus than pY-STAT1... - Determinants governing the potency of STAT3 activation via the individual STAT3-recruiting motifs of gp130Ute Lehmann
, , Pauwelsstrasse 30, D-52074 Aachen, Germany
Cell Signal 18:40-9. 2006..However, the potency of a specific motif to activate STAT3 directly reflects the affinity for the binding of STAT3 to this motif... 
SHPS-1/SIRP1alpha contributes to interleukin-6 signallingRadoslaw M Sobota
Department of Biochemistry, RWTH Aachen University, Pauwelsstrasse 30, D 52074 Aachen, Germany
Cell Signal 20:1385-91. 2008..Our observations will help to understand the tight balance of MAPK- and STAT3-activation in response to IL-6 which was found to be misbalanced in many autoimmune diseases, inflammatory proliferative diseases and cancer...- Novel inhibitors for murine and human leukemia inhibitory factor based on fused soluble receptorsSilke Metz
Institut fur Biochemie, Universitätsklinikum RWTH Aachen, Pauwelsstrasse 30, Aachen, Germany
J Biol Chem 283:5985-95. 2008..The gained knowledge on the construction of LIF inhibitors can be transferred to the design of inhibitors for related cytokines such as IL-31, IL-27, and oncostatin M for the treatment of inflammatory and malignant diseases... - Oncostatin M-induced activation of stress-activated MAP kinases depends on tyrosine 861 in the OSM receptor and requires Jak1 but not Src kinasesIrene Böing
Institut fur Biochemie, Universitätsklinikum der Rheinisch Westfälischen Technischen Hochschule Aachen, Pauwelsstr 30, 52074 Aachen, Germany
Cell Signal 18:50-61. 2006..Erk1/2 activation is negatively influenced by p38 activation and inhibition of p38 significantly prolongs the half-life of OSM-induced Egr-1... - A fusion protein of the gp130 and interleukin-6Ralpha ligand-binding domains acts as a potent interleukin-6 inhibitorCecile Ancey
Institut fur Biochemie, Universitätsklinikum Rheinisch Westfälische Technische Hochschule Aachen, Pauwelsstrasse 30, 52057 Aachen, Germany
J Biol Chem 278:16968-72. 2003..The fusion protein strategy presented here can also be applied to other cytokines that signal via receptors composed of two different subunits to design new potent inhibitors for anti-cytokine therapies... - Prostaglandin E1 inhibits IL-6-induced MCP-1 expression by interfering specifically in IL-6-dependent ERK1/2, but not STAT3, activationRadoslaw M Sobota
Department of Biochemistry, Medical School, RWTH Aachen University, Pauwelsstrasse 30, 52074 Aachen, Germany
Biochem J 412:65-72. 2008..In summary, we have discovered a specific cross-talk between the adenylate cyclase cascade and the IL-6-induced MAPK (mitogen-activated protein kinase) cascade and have investigated its impact on IL-6-dependent gene expression... - Orientational constraints of the gp130 intracellular juxtamembrane domain for signalingJens S Greiser
, , Pauwelsstrasse 30, Aachen 52074, Germany
J Biol Chem 277:26959-65. 2002..We suggest a new model concerning the gp130 activation mode in which the relative orientation of the cytoplasmic regions seems to be critical for further signal transduction... - A functional role of the membrane-proximal extracellular domains of the signal transducer gp130 in heterodimerization with the leukemia inhibitory factor receptorAndreas Timmermann
Institut fur Biochemie, Rheinisch Westfälische Technische Hochschule Aachen, Germany
Eur J Biochem 269:2716-26. 2002.... - Signal transducer and activator of transcription STAT3 plays a major role in gp130-mediated acute phase protein gene activationPetra May
Department of Biochemistry, Universitatsklinikum, Rheinisch Westfälische Technische Hochschule Aachen, Aachen, Germany
Acta Biochim Pol 50:595-601. 2003..These experiments indicate that amongst the STAT factors known to be activated by IL-6 STAT3 is the most potent activator of acute-phase gene transcription... - SHP2 and SOCS3 contribute to Tyr-759-dependent attenuation of interleukin-6 signaling through gp130Ute Lehmann
Department of Biochemistry, Rheinisch Westfälische Technische Hochschule Aachen, Pauwelsstrasse 30, Aachen D 52074, Germany
J Biol Chem 278:661-71. 2003..These data suggest, that there are two, largely distinct modes of negative regulation of gp130 activity, despite the fact that both SOCS3 and SHP2 are recruited to the same site within gp130... - Constitutive suppressor of cytokine signaling 3 expression confers a growth advantage to a human melanoma cell lineWaraporn Komyod
Institut fur Biochemie, Universitätsklinikum der Rheinisch Westfälischen Technischen Hochschule Aachen, Germany
Mol Cancer Res 5:271-81. 2007..However, in situ analysis of human melanoma specimens revealed SOCS3 immunoreactivity in 3 out of 10 samples, suggesting that in vivo SOCS3 may possibly play a role in IL-6 resistance in at least a fraction of tumors... - Interleukin-6 plays a crucial role in the hepatic expression of SOCS3 during acute inflammatory processes in vivoXiang Ping Yang
Department of Biochemistry, Medical School, RWTH Aachen, Pauwelsstrasse 30, 52074 Aachen, Germany
J Hepatol 43:704-10. 2005..The individual contribution of each cytokine to the induction of SOCS3 in vivo is unknown... - Development of an IL-6 inhibitor based on the functional analysis of murine IL-6Ralpha(1)Monique Y Wiesinger
Institut fur Biochemie, Universitätsklinikum RWTH Aachen, Aachen 52074, Germany
Chem Biol 16:783-94. 2009..mIL-6-RFP will permit further characterization of the role of IL-6 in various disease models and could ultimately lead to anti-IL-6 therapy... - Characterization of the signaling capacities of the novel gp130-like cytokine receptorAlexandra Dreuw
Institut fur Biochemie, Universitätsklinikum der Rheinisch Westfälischen Technischen Hochschule Aachen, Pauwelsstrasse 30, 52074 Aachen, Germany
J Biol Chem 279:36112-20. 2004..We propose that this is due to a lack of recruitment of the tyrosine phosphatase SHP-2 or the adaptor protein Shc to the cytoplasmic domain of GPL... - Novel role of Janus kinase 1 in the regulation of oncostatin M receptor surface expressionSimone Radtke
Institut fur Biochemie, Universitätsklinikum der Rheinisch Westfälischen Technischen Hochschule Aachen, Pauwelsstr 30, 52074 Aachen, Germany
J Biol Chem 277:11297-305. 2002..Finally we demonstrate that in Jak1-deficient cells, the endogenous OSMR is significantly down-regulated, an effect that can be reversed by transient expression of Jak1 in these cells... - Interleukin-6 is a direct mediator of T cell migrationManuela Weissenbach
Department of Biochemistry, RWTH Aachen, Aachen, Germany
Eur J Immunol 34:2895-906. 2004..Selective activation of the JAK/STAT or the MAPK cascade by mutated receptor proteins shows a crucial role of IL-6-initiated SH2 domain-containing tyrosine phosphatase 2/MAPK activity for migration... - Box 2 region of the oncostatin M receptor determines specificity for recruitment of Janus kinases and STAT5 activationChristoph Hintzen
Institut fur Biochemie, Universitätsklinikum RWTH Aachen, Pauwelsstrasse 30, 52074 Aachen, Germany
J Biol Chem 283:19465-77. 2008.... - Akt modulates STAT3-mediated gene expression through a FKHR (FOXO1a)-dependent mechanismMarcin Kortylewski
, RWTH Aachen, 52057 Aachen, Germany
J Biol Chem 278:5242-9. 2003..Our results indicate that FKHR can modulate the IL-6-induced transcriptional activity by acting as a coactivator of STAT3... - Structural requirements of the interleukin-6 signal transducer gp130 for its interaction with Janus kinase 1: the receptor is crucial for kinase activationClaude Haan
Department of Biochemistry, Rheinisch Westfalische Technische Hochschule, Aachen, Pauwelsstrasse 30, 52074 Aachen, Germany
Biochem J 361:105-11. 2002.... - Characterization of methylthioadenosin phosphorylase (MTAP) expression in malignant melanomaIris Behrmann
Institute of Biochemistry, RWTH Aachen, Aachen, Germany
Am J Pathol 163:683-90. 2003..This finding may be of great clinical significance because recently an association between MTAP activity and interferon sensitivity has been suggested... - Mesangial cell gelatinase A synthesis is attenuated by oscillating hyperbaric pressureAbdelaziz En-Nia
Division of Nephrology and Immunology, Medical Clinic II, RWTH Aachen, Pauwelsstrasse 30, 52057 Aachen, Germany
Biochem J 362:693-700. 2002..In conclusion, hyperbaric OP elicits time-dependent changes in rat MC gelatinase A gene transcription... - TNF-alpha induces tyrosine phosphorylation and recruitment of the Src homology protein-tyrosine phosphatase 2 to the gp130 signal-transducing subunit of the IL-6 receptor complexJohannes G Bode
Klinik fur Gastroenterologie, Hepatologie und Infektiologie, Medizinische Klinik der Heinrich Heine Universität, Dusseldorf, Germany
J Immunol 171:257-66. 2003..Furthermore, activation of p38 mitogen-activated protein kinase is shown to be essential for the inhibitory effect of TNF-alpha on IL-6 signaling and TNF-alpha-dependent recruitment of SHP2 to gp130... - Activation of NF-kappaB by IL-1beta blocks IL-6-induced sustained STAT3 activation and STAT3-dependent gene expression of the human gamma-fibrinogen geneUte Albrecht
Clinic for Gastroenterology, Hepatology and Infectiology, Heinrich Heine University, 40255 Düsseldorf, Germany
Cell Signal 19:1866-78. 2007.... - A new high affinity binding site for suppressor of cytokine signaling-3 on the erythropoietin receptorMichael Hortner
Bayer Pharma Research Center, Wuppertal, Germany
Eur J Biochem 269:2516-26. 2002.... - Interleukin-6 regulates hepatic transporters during acute-phase responseElmar Siewert
Department of Internal Medicine III, Aachen University RWTH, Aachen, Germany
Biochem Biophys Res Commun 322:232-8. 2004..IL-6 is required for transporter down-regulation during aseptic inflammation. Furthermore, IL-6 also contributes to transporter regulation during LPS-induced cholestasis at more delayed time points... - Dual role of the Jak1 FERM and kinase domains in cytokine receptor binding and in stimulation-dependent Jak activationSerge Haan
Life Science Research Unit, Faculte des Sciences, de la Technologie et de la Communication, Université du Luxembourg, Luxembourg
J Immunol 180:998-1007. 2008..Our data show that the structural integrity of both the FERM domain and of the kinase domain is essential for both receptor binding and catalytic function/autoinhibition... - Interleukin-6-type cytokines upregulate expression of multidrug resistance-associated proteins in NHEK and dermal fibroblastsAlexandra Dreuw
Department of Biochemistry, University Hospital, Aachen, Germany
J Invest Dermatol 124:28-37. 2005..Several inflammatory skin diseases show an enhanced expression of IL-6-type cytokines. Correspondingly, upregulation of MRP expression was found in lesional skin taken from patients with psoriasis and lichen planus... - Activation of STAT3 by IL-6 and IL-10 in primary human macrophages is differentially modulated by suppressor of cytokine signaling 3Claudia Niemand
Institut für Biochemie and Klinik und Lehrstuhl für Anästhesiologie, Universitätsklinikum RWTH Aachen, Aachen, Germany
J Immunol 170:3263-72. 2003.... - Tyrosine phosphorylation disrupts elongin interaction and accelerates SOCS3 degradationSerge Haan
Department of Immunology, Queen s University Belfast, 97 Lisburn Road, Belfast BT9 7BL, Northern Ireland
J Biol Chem 278:31972-9. 2003..The data suggest that interaction with elongin C stabilizes SOCS3 protein expression and that phosphorylation of SOCS box tyrosine residues disrupts the complex and enhances proteasome-mediated degradation of SOCS3... - Signaling through a mutant IFN-gamma receptorAna P Costa-Pereira
Cancer Research UK, London
J Immunol 175:5958-65. 2005..Data from different cell types further emphasizes the importance of cellular background in determining the response... - STAT5 contributes to interferon resistance of melanoma cellsClaudia Wellbrock
Department of Physiological Chemistry I, Biocenter, Theodor Boveri Institute, University of Wurzburg, Am Hubland, 97074 Wurzburg, Germany
Curr Biol 15:1629-39. 2005..Although advanced melanomas clinically resistant to IFNalpha are frequently characterized by inefficient STAT1 signaling, the mechanisms underlying advanced-stage interferon resistance are poorly understood... - ME3738 protects from concanavalin A-induced liver failure via an IL-6-dependent mechanismChristian Klein
Department of Gastroenterology, Hepatology and Endocrinology, Medizinische Hochschule Hannover, Hannover, Germany
Eur J Immunol 33:2251-61. 2003..Therefore, we demonstrate that ME3738 triggers IL-6 expression, which activates pathways that are relevant to protect from Con A-induced liver failure... - Polarity and lipid raft association of the components of the ciliary neurotrophic factor receptor complex in Madin-Darby canine kidney cellsDeborah M Buk
Institut fur Biologische Chemie und Ernahrungswissenschaft, Universitat Hohenheim, Garbenstrasse 30, 70599 Stuttgart, Germany
J Cell Sci 117:2063-75. 2004..CNTF-, LIF-, and IL-6-dependent STAT3 activation was sensitive to the cholesterol-depleting drug methyl-beta-cyclodextrin (MCD) suggesting that the integrity of lipid rafts is important for IL-6-type cytokine-induced STAT activation... - Bow to your partner for signalingHeike M Hermanns
Nat Struct Mol Biol 12:476-8. 2005 - Functional expression of the interleukin-11 receptor alpha-chain and evidence of antiapoptotic effects in human colonic epithelial cellsStephan Kiessling
Department of Internal Medicine I, University of Regensburg, Germany
J Biol Chem 279:10304-15. 2004..The beneficial effects of IL-11 therapy are likely to be mediated by CEC via activation of the Akt-survival pathway, mediating antiapoptotic effects to support mucosal integrity... - Cell density dependent increase of constitutive signal transducers and activators of transcription 3 activity in melanoma cells is mediated by Janus kinasesStephanie Kreis
Laboratoire de Biologie et Physiologie Intégrée, University of Luxembourg, 162A Avenue de la Faïencerie, L 1511 Luxembourg, Luxembourg
Mol Cancer Res 5:1331-41. 2007....