HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Schmitz, J. Articles by Schaper, F. Search for Related Content PubMed PubMed Citation Articles by Schmitz, J. Articles by Schaper, F.

The Cytoplasmic Tyrosine Motifs in Full-Length Glycoprotein 130 Have Different Roles in IL-6 Signal Transduction¹

Institut für Biochemie Rheinisch-Westfälische Technische Hochschule \E (RWTH), Aachen, Germany

The function of the signal-transducing receptor subunit glycoprotein 130 (gp130) in the IL-6-receptor complex has previously been studied using carboxyl-terminal deletion mutants or a truncated molecule of 60 membrane-proximal amino acids (containing box 1 and box 2) linked to the individual gp130 tyrosine motifs. However, the redundancy of the tyrosine motifs within the cytoplasmic part of gp130 has been neglected. Here we describe the analysis of the function of the individual cytoplasmic tyrosine residues of gp130 in the context of the full-length receptor protein in IL-6 signaling as measured by STAT activation, acute phase protein induction, and stimulation of proliferation. Add-back receptor mutants containing only one cytoplasmic tyrosine have been generated and tested for their efficiency in IL-6 signal transduction. Our studies revealed that tyrosine motifs which have been described to recruit STAT proteins are not equivalent with respect to their potential to activate STAT factors and acute phase protein gene promoters: the two distal tyrosines, Tyr⁹⁰⁵ and Tyr⁹¹⁵, of gp130 were more potent than Tyr⁷⁶⁷ and Tyr⁸¹⁴. Surprisingly, Tyr⁹⁰⁵ and Tyr⁹¹⁵ mediate acute phase protein gene promoter activation stronger than the wild-type receptor containing all six cytoplasmic tyrosine residues. In contrast, Ba/F3 cells stably transfected with add-back receptors containing Tyr⁷⁶⁷ or Tyr⁹⁰⁵ were more sensitive to IL-6-induced proliferation than cells expressing the other add-back receptor mutants. Thus, the tyrosine residues in the cytoplasmic part of gp130 were found to contribute differentially to IL-6 signal transduction in the full- length gp130 protein.

This article has been cited by other articles:

				G. D. Kalliolias and L. B. Ivashkiv IL-27 Activates Human Monocytes via STAT1 and Suppresses IL-10 Production but the Inflammatory Functions of IL-27 Are Abrogated by TLRs and p38 J. Immunol., May 1, 2008; 180(9): 6325 - 6333. [Abstract] [Full Text] [PDF]

				C. Ehlting, W. S. Lai, F. Schaper, E. D. Brenndorfer, R.-J. Matthes, P. C. Heinrich, S. Ludwig, P. J. Blackshear, M. Gaestel, D. Haussinger, et al. Regulation of Suppressor of Cytokine Signaling 3 (SOCS3) mRNA Stability by TNF-{alpha} Involves Activation of the MKK6/p38MAPK/MK2 Cascade J. Immunol., March 1, 2007; 178(5): 2813 - 2826. [Abstract] [Full Text] [PDF]

				F. Hu and J. Nicholas Signal Transduction by Human Herpesvirus 8 Viral Interleukin-6 (vIL-6) Is Modulated by the Nonsignaling gp80 Subunit of the IL-6 Receptor Complex and Is Distinct from Signaling Induced by Human IL-6 J. Virol., November 1, 2006; 80(21): 10874 - 10878. [Abstract] [Full Text] [PDF]

				U. Sommer, C. Schmid, R. M. Sobota, U. Lehmann, N. J. Stevenson, J. A. Johnston, F. Schaper, P. C. Heinrich, and S. Haan Mechanisms of SOCS3 Phosphorylation upon Interleukin-6 Stimulation: CONTRIBUTIONS OF Src- AND RECEPTOR-TYROSINE KINASES J. Biol. Chem., September 9, 2005; 280(36): 31478 - 31488. [Abstract] [Full Text] [PDF]

				B. Chen, S. Tsui, and T. J. Smith IL-1{beta} Induces IL-6 Expression in Human Orbital Fibroblasts: Identification of an Anatomic-Site Specific Phenotypic Attribute Relevant to Thyroid-Associated Ophthalmopathy J. Immunol., July 15, 2005; 175(2): 1310 - 1319. [Abstract] [Full Text] [PDF]

				X.-P. Yang, U. Albrecht, V. Zakowski, R. M. Sobota, D. Haussinger, P. C. Heinrich, S. Ludwig, J. G. Bode, and F. Schaper Dual Function of Interleukin-1{beta} for the Regulation of Interleukin-6-induced Suppressor of Cytokine Signaling 3 Expression J. Biol. Chem., October 22, 2004; 279(43): 45279 - 45289. [Abstract] [Full Text] [PDF]

				L. Zhao, S. Hart, J. Cheng, J. J. Melenhorst, B. Bierie, M. Ernst, C. Stewart, F. Schaper, P. C. Heinrich, A. Ullrich, et al. Mammary Gland Remodeling Depends on gp130 Signaling through Stat3 and MAPK J. Biol. Chem., October 15, 2004; 279(42): 44093 - 44100. [Abstract] [Full Text] [PDF]

				B. Giese, C.-K. Au-Yeung, A. Herrmann, S. Diefenbach, C. Haan, A. Kuster, S. B. Wortmann, C. Roderburg, P. C. Heinrich, I. Behrmann, et al. Long Term Association of the Cytokine Receptor gp130 and the Janus Kinase Jak1 Revealed by FRAP Analysis J. Biol. Chem., October 3, 2003; 278(40): 39205 - 39213. [Abstract] [Full Text] [PDF]

				C. Niemand, A. Nimmesgern, S. Haan, P. Fischer, F. Schaper, R. Rossaint, P. C. Heinrich, and G. Muller-Newen Activation of STAT3 by IL-6 and IL-10 in Primary Human Macrophages Is Differentially Modulated by Suppressor of Cytokine Signaling 3 J. Immunol., March 15, 2003; 170(6): 3263 - 3272. [Abstract] [Full Text] [PDF]

				D. E. Isaksen, H. Baumann, B. Zhou, S. Nivollet, A. G. Farr, S. D. Levin, and S. F. Ziegler Uncoupling of Proliferation and Stat5 Activation in Thymic Stromal Lymphopoietin-Mediated Signal Transduction J. Immunol., April 1, 2002; 168(7): 3288 - 3294. [Abstract] [Full Text] [PDF]

				M. Schaeffer, M. Schneiderbauer, S. Weidler, R. Tavares, M. Warmuth, G. de Vos, and M. Hallek Signaling through a Novel Domain of gp130 Mediates Cell Proliferation and Activation of Hck and Erk Kinases Mol. Cell. Biol., December 1, 2001; 21(23): 8068 - 8081. [Abstract] [Full Text] [PDF]

				S. Pflanz, I. Kurth, J. Grotzinger, P. C. Heinrich, and G. Muller-Newen Two Different Epitopes of the Signal Transducer gp130 Sequentially Cooperate on IL-6-Induced Receptor Activation J. Immunol., December 15, 2000; 165(12): 7042 - 7049. [Abstract] [Full Text] [PDF]

				D. Anhuf, M. Weissenbach, J. Schmitz, R. Sobota, H. M. Hermanns, S. Radtke, S. Linnemann, I. Behrmann, P. C. Heinrich, and F. Schaper Signal Transduction of IL-6, Leukemia-Inhibitory Factor, and Oncostatin M: Structural Receptor Requirements for Signal Attenuation J. Immunol., September 1, 2000; 165(5): 2535 - 2543. [Abstract] [Full Text] [PDF]

				H. M. Hermanns, S. Radtke, F. Schaper, P. C. Heinrich, and I. Behrmann Non-redundant Signal Transduction of Interleukin-6-type Cytokines. THE ADAPTER PROTEIN Shc IS SPECIFICALLY RECRUITED TO THE ONCOSTATIN M RECEPTOR J. Biol. Chem., December 22, 2000; 275(52): 40742 - 40748. [Abstract] [Full Text] [PDF]