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Sonderforschungsbereich 415:
"Specifity and Pathophysiology of Signal Transduction Pathways"
at Christian-Albrechts-University in Kiel
Project B7: »Solution structure of interleukin-6-receptor and gp130-extracellular domains by NMR-spectroscopy«
Summary
The transmembrane glycoprotein gp130 is the common signal transducing receptor subunit of the interleukin-6-type cytokines (IL-6, CNTF, LIF, OSM, CT-1 und IL-11). It is a member of the cytokine-receptor superfamily predicted to consist of six domains in its extracellular part. It is known that the three N-terminal domains are involved in binding to the IL-6/IL-6R complex and the three C-terminal domains are crucial for signal initiation. The structural determinants and mechanisms for the initiation of the signal are still not understood. However, the aim of this project is to solve the structure of IL-6R and gp130 domains by multi-dimensional heteronuclear magnetic resonance (NMR)-spectroscopy and the definition of the interdomain interactions.
Original papers
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Veldman, C.M., Gebhard, K.L., Uter, W., Wassmuth, R., Grötzinger, J., Schultz, E., Hertl, M (2004)
 T cell recognition of desmoglein 3 peptides in patients with pemphigus vulgaris and healthy individuals |
| J Immun, in press |
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Aasland, D., Schuster, B., Grötzinger, J., Rose-John, S., Kallen, K.-J. (2003)
Analysis of the leukemia inhibitory factor receptor functional domains by chimeric receptors and cytokines. |
| Biochemistry. 42:5244-52 |
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Harmengies, D., Wang, XM, Vandenbussche, P., Leon, A., Vusio, P., Grötzinger, J., Jacques, Y., Goormaghtigh, E., Devreese, B., and Content, J. (2003)
Characterization of a potent human interleukin-11 agonist |
| Biochem J 375, 23-32 |
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Schuster, B., Kovaleva, M., Sun, Y., Regenhard, P., Matthews, V., Grötzinger, J., Rose-John, S., Kallen, K.-J. (2003)
Signalling of human CNTF revisited: the interleukin-6 (IL-6) receptor can serve as an a-receptor for ciliary neurotrophic factor (CNTF). |
| J Biol Chem. 278:9528-9535 |
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Schwantner, A., Dingley, A. J., Özbek, S., Hecht, O., Rose-John, S. and Grötzinger, J. (2003)
1H, 15N and 13C backbone assignment of the carboxyl terminal domain of the cytokine binding module of the interleukin-6 receptor. |
| J Biomol NMR. in press |
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Schwantner, A., Dingley, A. J., Özbek, S., Rose-John, S. and Grötzinger, J. (2003)
Direct determination of the interleukin-6 binding epitope of the interleukin-6 receptor by NMR spectroscopy. |
| J Biol Chem., in press |
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Wiechmann, S., Czajkowska, H., de Graaf, K., Grötzinger, J., Joost, H.G., Becker, W. (2003)
Unusual function of the activation loop in the protein kinase DYRK1A |
| Biochem Biophys Res Commun 302, 403-408 |
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Aasland, D., Oppmann, B., Grötzinger, J., Rose-John, S., Kallen, K.-J. (2002)
The upper cytokine binding module and the Ig-like domain of the LIFR are sufficient for a functional LIFR complex. |
| J Mol Biol 315:637-646 |
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Althoff, K., Müllberg, J., Aasland, D., Voltz, N., Kallen, K.J., Grötzinger, J., Rose-John, S. (2001)
Recognition Sequences and Structural Elements Contribute to Shedding Susceptibility of Membrane Proteins |
| Biochem. J. 353, 663-672 |
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Haan, C., Isharc, H., Hermanns, H.M., Schmitz-van de Leur, H., Kerr, I.M., (2001)
Mapping of a region within the N-terminus of JAK1 involved in cytokine receptor interaction |
| J Biol Chem. 276, 37451-37458 |
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Himpel, S., Panzer, P., Eirmbter, K., Czajkowska, H., Sayed, M., Packman, L.C., Blundell, T., Kentrup, H., Grötzinger, J., Joost, H.G., Becker, W. (2001)
Identification of the autophosphorylation sites and characterization of their effects in the dual-specificity protein kinase DYRK1A |
| Biochem. J. 359, 497-505 |
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Kernebeck, T., Lohse, A.W., Grötzinger, J. (2001)
A bioinformatical approach reveals the function of the autoimmune hepatitis target antigen SLA / LP. |
| Hepatol. 34, 230-234. |
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Pflanz, S., Kernebeck, T., Giese, B., Herrmann, A., Pachta-Nick, M., Stahl, J., Wollmer, A., Heinrich, PC., Müller-Newen, G., Grötzinger, J. (2001)
The signal transducer gp130: Biochemical characterization of the three membrane-proximal extracellular domains and studies on their oligomerization potential |
| Biochem. J. 356, 605-612 |
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Schleinkofer, K., Dingley, A., Tacken, I., Federwisch, M., Müller-Newen, G., Heinrich, P.C., Vusio, P., Jacques, Y., Grötzinger, J. (2001)
Identification of the domain in the Interleukin-11 Receptor that mediates ligand binding |
| J. Mol. Biol. 306, 263-274 |
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Reviews
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Grötzinger, J. (2002)
Molecular Mechanisms of cytokine receptor activation |
| Biophys Biochem Acta 1592, 215-223 |
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