Stefan Düsterhöft
RWTH Aachen University
EctodomainProtein–protein interactionTransmembrane domainSheddaseGlycoprotein 130Cleavage (embryo)InternalizationMembrane proteinCellMolecular biologyPhagocytosisCell adhesion moleculeProinflammatory cytokinePeptide sequenceReceptorTumor necrosis factor alphaProteasesChemistrySmall hairpin RNAInterleukin-6 receptorTransmembrane proteinProteaseCell membraneDisintegrinADAM10PhosphatidylserineProteolysisExtracellularADAM ProteinsADAM17 ProteinCancer researchRhomboidBiochemistryMetalloproteinaseSignal transductionSecretory pathwayTranscription factorBiologyCell biology
22Publications
11H-index
457Citations
Publications 22
Newest
#1Stefan Düsterhöft (RWTH Aachen University)H-Index: 11
#2Selcan Kahveci-Türköz (RWTH Aachen University)
Last. Andreas Ludwig (RWTH Aachen University)H-Index: 35
view all 14 authors...
Membrane-tethered signalling proteins such as TNFα and many EGF receptor ligands undergo shedding by the metalloproteinase ADAM17 to get released. The pseudoproteases iRhom1 and iRhom2 are important for the transport, maturation and activity of ADAM17. Yet, the structural and functional requirements to promote the transport of the iRhom-ADAM17 complex have not yet been thoroughly investigated. Utilising in silico and in vitro methods, we here map the conserved iRhom homology domain (IRHD) and pr...
Source
#1Lydia Koch (CAU: University of Kiel)H-Index: 1
#2Birte Kespohl (Otto-von-Guericke University Magdeburg)H-Index: 1
Last. Christoph Garbers (Otto-von-Guericke University Magdeburg)H-Index: 32
view all 8 authors...
Interleukin-11 (IL-11) is a pleiotropic cytokine with both pro- and anti-inflammatory properties. It activates its target cells via binding to the membrane-bound IL-11 receptor (IL-11R), which then recruits a homodimer of the ubiquitously expressed, signal-transducing receptor gp130. Besides this classic signaling pathway, IL-11 can also bind to soluble forms of the IL-11R (sIL-11R), and IL-11/sIL-11R complexes activate cells via the induction of gp130 homodimerization (trans-signaling). We have...
1 CitationsSource
#1Tanzeela Awan (RWTH Aachen University)H-Index: 1
#2Aaron Babendreyer (RWTH Aachen University)H-Index: 8
Last. Andreas Ludwig (RWTH Aachen University)H-Index: 63
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Hepatocellular carcinoma (HCC) is one of the most common metastatic tumours. Tumour growth and metastasis depend on the induction of cell proliferation and migration by various mediators. Here, we report that the A Disintegrin and Metalloproteinase (ADAM) 8 is highly expressed in murine HCC tissues as well as in murine and human hepatoma cell lines Hepa1-6 and HepG2, respectively. To establish a dose-dependent role of different ADAM8 expression levels for HCC progression, ADAM8 expression was ei...
1 CitationsSource
#1Anke Seifert (RWTH Aachen University)H-Index: 3
#2Stefan Düsterhöft (RWTH Aachen University)H-Index: 11
Last. Andreas Ludwig (RWTH Aachen University)H-Index: 63
view all 10 authors...
The metalloproteinase ADAM10 critically contributes to development, inflammation, and cancer and can be controlled by endogenous or synthetic inhibitors. Here, we demonstrate for the first time that loss of proteolytic activity of ADAM10 by either inhibition or loss of function mutations induces removal of the protease from the cell surface and the whole cell. This process is temperature dependent, restricted to mature ADAM10, and associated with an increased internalization, lysosomal degradati...
3 CitationsSource
#1Charlotte M. Flynn (CAU: University of Kiel)H-Index: 6
#2Birte Kespohl (Otto-von-Guericke University Magdeburg)H-Index: 1
Last. Christoph Garbers (Otto-von-Guericke University Magdeburg)H-Index: 32
view all 10 authors...
Abstract Interleukin-6 (IL-6) is a cytokine implicated in pro-inflammatory as well as regenerative processes and acts via receptor complexes consisting of the ubiquitously expressed, signal-transducing receptor gp130 and the IL-6 receptor (IL-6R). The IL-6R is expressed only on hepatocytes and subsets of leukocytes, where it mediates specificity of the receptor complex to IL-6 as the subunit gp130 is shared with all other members of the IL-6 cytokine family like IL-11 or IL-27. The amount of IL-...
2 CitationsSource
#1Charlotte M. Flynn (CAU: University of Kiel)H-Index: 6
#2Yvonne Garbers (CAU: University of Kiel)H-Index: 9
Last. Christoph Garbers (Otto-von-Guericke University Magdeburg)H-Index: 32
view all 12 authors...
The cytokine interleukin-6 (IL-6) fulfills its pleiotropic functions via different modes of signaling. Regenerative and anti-inflammatory activities are mediated via classic signaling, in which IL-6 binds to the membrane-bound IL-6 receptor (IL-6R). For IL-6 trans-signaling, which accounts for the pro-inflammatory properties of the cytokine, IL-6 activates its target cells via soluble forms of the IL-6R (sIL-6R). We have previously shown that the majority of sIL-6R in human serum originates from...
1 CitationsSource
#1Aaron BabendreyerH-Index: 8
#2Diana M. Rojas-González (TUM: Technische Universität München)H-Index: 1
Last. Andreas LudwigH-Index: 35
view all 7 authors...
Background: Endothelial function significantly depends on the proteolytic release of surface expressed signal molecules, their receptors and adhesion molecules via the metalloproteinase ADAM17. The pseudoproteases iRhom1 and 2 independently function as adapter proteins for ADAM17 and are essential for the maturation, trafficking, and activity regulation of ADAM17. Bioinformatic data confirmed that immune cells predominantly express iRhom2 while endothelial cells preferentially express iRhom1. Ob...
1 CitationsSource
#1Anke Seifert (RWTH Aachen University)H-Index: 3
#2Justyna Wozniak (RWTH Aachen University)H-Index: 3
Last. Andreas Ludwig (RWTH Aachen University)H-Index: 63
view all 9 authors...
Uptake of bacteria by phagocytes is a crucial step in innate immune defence. Members of the disintegrin and metalloproteinase (ADAM) family critically control the immune response by limited proteolysis of surface expressed mediator molecules. Here, we investigated the significance of ADAM17 and its regulatory adapter molecule iRhom2 for bacterial uptake by phagocytes. Inhibition of metalloproteinase activity led to increased phagocytosis of pHrodo labelled Gram-negative and -positive bacteria (E...
2 CitationsSource
#1Stefan Düsterhöft (RWTH Aachen University)H-Index: 11
#2Anne-Kathrin Bartels (CAU: University of Kiel)H-Index: 3
Last. Inken LorenzenH-Index: 24
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Proteolytic processing of membrane proteins by A disintegrin and metalloprotease-17 (ADAM17) is a key regulatory step in many physiological and pathophysiological processes. This so-called shedding is essential for development, regeneration and immune defense. An uncontrolled ADAM17 activity promotes cancer development, chronic inflammation and autoimmune diseases. Consequently, the ADAM17 activity is tightly regulated. As a final trigger for the shedding event a phosphatidylserine (PS) flip to ...
1 CitationsSource
#1Christopher Platen (Boston Children's Hospital)H-Index: 4
#2Stephan Dreschers (Boston Children's Hospital)H-Index: 6
Last. Thorsten W. Orlikowsky (Boston Children's Hospital)H-Index: 16
view all 7 authors...
Neonates are extremely susceptible to bacterial infections, and evidences suggest that phagocytosis-induced cell death (PICD) is less frequently triggered in neonatal monocytes than in monocytes from adult donors. An insufficient termination of the inflammatory response, leading to a prolonged survival of neonatal monocytes with ongoing proinflammatory cytokine release, could be associated with the progression of various inflammatory diseases in neonates. Our previous data indicate that amphireg...
2 CitationsSource