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Keywords
(9)
Cytokine Receptors
Fusion Protein
Gene Delivery
Gene Therapy
Leukemia Inhibitory Factor
Transgenic Animals
Viral Vector
Ligand Binding Domain
Oncostatin M
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A receptor fusion protein for the inhibition of murine oncostatin M
A receptor fusion protein for the inhibition of murine oncostatin M,10.1186/1472-6750-11-3,BMC Biotechnology,Liv Brolund,Andrea Küster,Sabrina Korr,Mi
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A receptor fusion protein for the inhibition of murine oncostatin M
(
Citations: 1
)
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Liv Brolund
,
Andrea Küster
,
Sabrina Korr
,
Michael Vogt
,
Gerhard Müller-Newen
BACKGROUND: Most cytokines signal through heteromeric receptor complexes consisting of two or more different receptor subunits. Fusion proteins of the extracellular parts of receptor subunits turned out to be promising cytokine inhibitors useful in anti-cytokine therapy and cytokine research. RESULTS: We constructed receptor fusion proteins (RFP) consisting of the
ligand binding
domains of the murine
oncostatin M
(mOSM) receptor subunits mOSMR and mgp130 connected by a flexible linker as potential mOSM inhibitors. mgp130 is a shared cytokine receptor that is also used by other cytokines such as IL-6 and
leukemia inhibitory factor
(LIF). In this study we compare four types of mOSM-RFPs that contain either domains D1-D3 or domains D2-D3 of mgp130 and are arranged in two ways. Domain D1 of mgp130 turned out to be dispensable for mOSM-binding. However, the arrangement of the two receptor subunits is essential for the inhibitory activity. We found mOSM induced STAT3 phosphorylation to be suppressed only when the mOSMR fragment was fused in front of the mgp130 fragment. CONCLUSIONS: mOSM-RFP consisting of D1-D4 of mOSMR and D2-D3 of mgp130 is a highly potent and specific inhibitor of mOSM. Since mOSM-RFP is encoded by a single gene it offers numerous possibilities for specific cytokine inhibition in
gene delivery
approaches based on viral vectors,
transgenic animals
and finally gene therapy.
Journal:
BMC Biotechnology - BMC BIOTECHNOL
, vol. 11, no. 1, pp. 3-11, 2011
DOI:
10.1186/1472-6750-11-3
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References
(21)
A Fusion Protein of the gp130 and Interleukin6Ralpha Ligand-binding Domains Acts as a Potent Interleukin6 Inhibitor
(
Citations: 10
)
C. Ancey
Journal:
Journal of Biological Chemistry - J BIOL CHEM
, vol. 278, no. 19, pp. 16968-16972, 2003
Characterization of the Interleukin (IL)-6 Inhibitor IL6-RFP: FUSED RECEPTOR DOMAINS ACT AS HIGH AFFINITY CYTOKINE-BINDING PROTEINS
(
Citations: 7
)
S. Metz
,
M. Wiesinger
,
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,
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,
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,
G. Muller-Newen
Journal:
Journal of Biological Chemistry - J BIOL CHEM
, vol. 282, no. 2, pp. 1238-1248, 2006
Molecular and Functional Characterization of a Soluble Form of Oncostatin M/Interleukin31 Shared Receptor
(
Citations: 5
)
C. Diveu
,
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Journal:
Journal of Biological Chemistry - J BIOL CHEM
, vol. 281, no. 48, pp. 36673-36682, 2006
Definition and Characterization of an Inhibitor for Interleukin31
(
Citations: 3
)
E. Venereau
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,
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,
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,
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Journal:
Journal of Biological Chemistry - J BIOL CHEM
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Cytokine traps: multi-component, high-affinity blockers of cytokine action
(
Citations: 101
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Aris N. Economides
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James P. Fandl
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Frank Lee
http://academic.research.microsoft.com/io.ashx?type=5&id=33789347&selfId1=0&selfId2=0&maxNumber=12&query=
Journal:
Nature Medicine - NATURE MED
, vol. 9, no. 1, pp. 47-52, 2002
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Citations
(1)
Development of Hepatic Pseudotumors for Image-guided Interventional and Surgical Research in a Large Animal Model
Mark G. van Vledder
,
Lia Assumpcao
,
Sanjay Munireddy
,
Kartik Sehgal
,
Emad M. Boctor
,
Michael A. Choti
Journal:
Journal of Vascular and Interventional Radiology - J VASC INTERVEN RADIOL
, vol. 22, no. 10, pp. 1452-1456, 2011