Abstract
The family of Interleukin-6(IL-6)-type cytokines comprises IL-6, IL-11, leukemia inhibitory factor (LIF), oncostatin M (OSM), ciliary neurotrophic factor (CNTF), cardiotrophin-1 (CT-1) and the recently described novel neurotrophin-1/B-cell stimulatory factor 3/cardiotrophin-1-like cytokine. These cytokines play an important role in hematopoiesis, inflammation, the acute phase response, and bone and heart development as well as neurogenesis. The redundant effects can be attributed to the shared use of the common signal transducing receptor chain glycoprotein (gp) 130. Gp130 is homodimerized by IL-6 and IL-I I upon binding to their ligand-specific a-receptors. The other cytokines of this family trigger the heterodimerization of gp130 with LIF receptor (LIF-R) or the OSM-specific receptor (OSM-R).
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Lütticken, C., Wegenka, U. M., Yuan, J., Buschmann, J., Schindler C., Ziemiecki, A., Harpur, A.G., Wilks, A. F., Yasukawa, K., Taga, T., Kishimoto, T., Barbieri, G., Pellegrini, S., Sendtner, M., Heinrich, P. C., and Horn, F., 1994, Association of transcription factor APRF and protein kinase Jak 1 with the Interleukin-6 signal transducer gp 130.Science263: 89–92.
Stahl, N., Boulton, T. G., Farruggella, T., Ip, N. Y., Davis, S., Witthuhn, B. A., Quelle, F. W., Silvennoinen, O., Barbieri, G., Pellegrini, S., Ihle, N. J., and Yancopoulos G. D., 1994. Association and activation of Jak-Tyk kinases by CNTF-LIF-OSM-IL-6 f3 receptor components.Science263: 92–95.
Heinrich P. C., Behrmann I., Müller-Newen G., Schaper F., and Graeve L., 1998. Interleukin-6-type cytokine signalling through the gp130/Jak/STAT pathway.Biochem. J.334: 297–314.
Haspel R. L., Salditt-Georgieff M., and Darnell Jr., J. E., 1996.The rapid inactivation of nuclear tyrosine phosphorylated Statl depends upon a protein tyrosine phosphatase.EMBO J.15: 6262–6268.
Kim T. K. and Maniatis T., 1996. Regulation of interferon-gamma-activated STAT1 by the ubiquitin-proteasome pathway.Science273: 1717–1719.
Stahl N., Farruggella T. J., Boulton T. G., Zhong Z., Darnell Jr. J. E., and Yancopoulos G. D., 1995. Choice of STATs and other substrates specified by modular tyrosine-based motifs in cytokine receptors.Science267: 1349–1353.
Schaper F., Gendo C., Eck M., Schmitz J., Grimm C., Anhuf D., Kerr I. M., and Heinrich P. C., 1998. Activation of the protein tyrosine phosphatase SHP2 via the interleukin-6 signal transducing receptor protein gp130 requires tyrosine kinase Jakl and limits acute-phase protein expression.Biochem. J.335: 557–565.
Anhuf D., Weissenbach M., Schmitz J., Sobota R., Hermanns H. M., Radtke S., Linnemann S., Behrmann I., Heinrich P. C., and Schaper F., 2000. Signal transduction of IL-6, leukemia-inhibitory factor, and oncostatin M: structural receptor requirements for signal attenuation.J. Immunol.165: 2535–2543.
Endo T. A., Masuhara M., Yokouchi M., Suzuki R., Sakamoto H., Mitsui K., Matsumoto A., Tanimura S., Ohtsubo M., Misawa H., Miyazaki T., Leonor N., Taniguchi T., Fujita T., Kanakura Y., Komiya S., and Yoshimura A., 1997. A new protein containing an SH2 domain that inhibits JAK kinases.Nature387: 921–924
Starr R., Willson T. A., Viney E. M., Murray L.J., Rayner J. R., Jenkins B. J., Gonda T. J., Alexander W. S., Metcalf D., Nicola N. A., and Hilton D. J., 1997. A family of cytokine-inducible inhibitors of signalling.Nature387: 917–921.
Naka T., Narazaki M., Hirata M., Matsumoto T., Minamoto S., Aono A., Nishimoto N., Kajita T., Taga T., Yoshizaki K., Akira S., and Kishimoto T., 1997. Structure and function of a new STAT-induced STAT inhibitor.Nature387: 924–929.
Schmitz J., Weissenbach M., Haan S., Heinrich P. C., and Schaper F., 2000. SOCS3 exerts its inhibitory function on interleukin-6 signal transduction through the SHP2 recruitment site of gp130.J. Biol. Chem.275: 12848–12846.
Terstegen L., Gatsios P., Bode J. G., Schaper F., Heinrich P. C., and Graeve L., 2000. The inhibition of interleukin-6-dependent STAT activation by mitogen-activated protein kinases depends on tyrosine-759 in the cytoplasmic tail of gp 130.J. Biol. Chem.275: 18810–18817.
Chung C. D., Liao J. Y., Liu B., Rao X. P., Jay P., Berta P., and Shuai K., 1997. Specific inhibition of Stat3 signal transduction by PIAS3.Science278: 1803–1805.
Rödel B., Tavassoli K., Karsunky H., Schmidt T., Bachmann M., Schaper F., Heinrich P., Shuai K., Elsässer H. P., and Möroy T., 2000. The zinc finger protein gfi-1 can enhance STAT3 signaling by interacting with the STAT3 inhibitor PIAS3.EMBO J.19: 5845–5855.
Dittrich E., Haft C. R., Muys L., Heinrich P. C., and Graeve L., 1996. A di-leucine motif and an upstream serine in the interleukin-6 (IL-6) signal transducer gp130 mediate ligand-induced endocytosis and down-regulation of the IL-6 receptor.J Biol. Chem.271: 5487–5494
Thiel S., Behrmann I., Dittrich E., Muys L., Tavernier J., Wijdenes J., Heinrich P. C., and Graeve L. 1998. Internalization of the interleukin 6 signal transducer gp130 does not require activation of the Jak/STAT pathway.Biochem. 1330: 47–54.
Martens A. S., Bode J. G., Heinrich P. C., and Graeve L., 2000. The cytoplasmic domain of the interleukin-6 receptor gp80 mediates its basolateral sorting in polarized madin-darby canine kidney cells.J. Cell. Sci.113: 3593–3602.
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Heinrich, P.C. et al. (2001). Termination and modulation of IL-6-type cytokine signaling. In: Mackiewicz, A., Kurpisz, M., Żeromski, J. (eds) Progress in Basic and Clinical Immunology. Advances in Experimental Medicine and Biology, vol 495. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-0685-0_20
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DOI: https://doi.org/10.1007/978-1-4615-0685-0_20
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