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Distinct roles for STAT1, STAT3, and STAT5 in differentiation gene induction and apoptosis inhibition by interleukin-9

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Demoulin, Jean-Baptiste [UCL] Van Roost, Emiel [UCL] Stevens, Monique Groner, Bernd Renauld, Jean-Christophe [UCL]

Interleukin-9 (IL-9) activates three distinct STAT proteins: STAT1, STAT3, and STAT5. This process depends on one tyrosine of the IL-9 receptor, which is necessary for proliferation, gene induction, and inhibition of apoptosis induced by glucocorticoids. By introduction of point mutations in amino acids surrounding this tyrosine, we obtained receptors that activated either STAT5 alone or both STAT1 and STAT3, thus providing us with the possibility to study the respective roles of these factors in the biological activities of IL-9. Both mutant receptors were able to prevent apoptosis, but only the mutant that activated STAT1 and STAT3 was able to support induction of granzyme A and L-selectin. In line with these results, constitutively activated STAT5 blocked glucocorticoid-induced apoptosis. In Ba/F3 cells, significant proliferation and pim-1 induction were observed with both STAT-restricted mutants, though proliferation was lower than with the wild-type receptor. These results suggest that survival and cell growth are redundantly controlled by multiple STAT factors, whereas differentiation gene induction is more specifically correlated with individual STAT activation by IL-9.

Document type Article de périodique (Journal article) – Article de recherche
Access type Accès restreint
Publication date 1999
Journal information "Journal of Biological Chemistry" - Vol. 274, no. 36, p. 25855-25861 (1999)
Peer reviewed yes
Publisher American Society for Biochemistry and Molecular Biology, Inc.
issn 0021-9258
e-issn 1083-351X
Publication status Publié
Affiliation UCL - MD/MIGE - Département de microbiologie, d'immunologie et de génétique
MESH Subject Animals ; Apoptosis - drug effects ; Cell Differentiation - drug effects ; Cell Line ; DNA-Binding Proteins - metabolism ; Gene Expression Regulation - drug effects ; Interleukin-9 - pharmacology ; Mice ; Milk Proteins ; Mutation ; STAT1 Transcription Factor ; STAT3 Transcription Factor ; STAT5 Transcription Factor ; Signal Transduction - drug effects ; Trans-Activators - metabolism
Links
  1. Demoulin, Cytokines Cell. Mol. Ther., 4, 243 (1998)
  2. Renauld, J. Leukocyte Biol., 57, 353 (1995)
  3. Demoulin J B, Uyttenhove C, Van Roost E, DeLestré B, Donckers D, Van Snick J, Renauld J C, A single tyrosine of the interleukin-9 (IL-9) receptor is required for STAT activation, antiapoptotic activity, and growth regulation by IL-9., 10.1128/mcb.16.9.4710
  4. Russell S., Johnston J., Noguchi M, Kawamura M, Bacon C., Friedmann M, Berg M, McVicar D., Witthuhn B., Silvennoinen O, et al., Interaction of IL-2R beta and gamma c chains with Jak1 and Jak3: implications for XSCID and XCID, 10.1126/science.7973658
  5. Higuchi, J. Immunol., 157, 297 (1996)
  6. Bauer Johannes H., Liu Kathleen D., You Yun, Lai Stephen Y., Goldsmith Mark A., Heteromerization of the γcChain with the Interleukin-9 Receptor α Subunit Leads to STAT Activation and Prevention of Apoptosis, 10.1074/jbc.273.15.9255
  7. Darnell Jr. J. E., STATs and Gene Regulation, 10.1126/science.277.5332.1630
  8. Greenlund, EMBO J., 13, 1591 (1994)
  9. Stahl N., Farruggella T., Boulton T., Zhong Z., Darnell J., Yancopoulos G., Choice of STATs and other substrates specified by modular tyrosine-based motifs in cytokine receptors, 10.1126/science.7871433
  10. Schindler Ulrike, Wu Pengguang, Rothe Mike, Brasseur Mike, McKnight Steven L., Components of a stat recognition code: Evidence for two layers of molecular selectivity, 10.1016/1074-7613(95)90013-6
  11. Rothman Paul, Kreider Brendt, Azam Mohammad, Levy David, Wegenka Ursula, Eilers Andreas, Decker Thomas, Horn Friedemann, Kashleva Helena, Ihle James, Schindler Chris, Cytokines and Growth factors signal through tyrosine phosphorylation of a family of related transcription factors, 10.1016/1074-7613(94)90088-4
  12. Demoulin Jean-Baptiste, Renauld Jean-Christophe, Interleukin 9 and its Receptor: An Overview of Structure and Function, 10.3109/08830189809043001
  13. Wakao, EMBO J., 13, 2182 (1994)
  14. Lin Jian-Xin, Migone Thi-Sau, Tseng Monica, Friedmann Michael, Weatherbee James A., Zhou Li, Yamauchi Akira, Bloom Eda T., Mietz Judy, John Susan, Leonard Warren J., The role of shared receptor motifs and common stat proteins in the generation of cytokine pleiotropy and redundancy by IL-2, IL-4, IL-7, IL-13, and IL-15, 10.1016/1074-7613(95)90141-8
  15. Leonard Warren J., O'Shea John J., JAKS AND STATS: Biological Implications, 10.1146/annurev.immunol.16.1.293
  16. Mizushima Seiichi, Nagata Shigekazu, pEF-BOS, a powerful mammalian expression vector, 10.1093/nar/18.17.5322
  17. Palacios Ronald, Steinmetz Michael, IL3-dependent mouse clones that express B-220 surface antigen, contain ig genes in germ-line configuration, and generate B lymphocytes in vivo, 10.1016/s0092-8674(85)80053-2
  18. Louahed, J. Immunol., 154, 5061 (1995)
  19. Yip-Scheider, Blood, 85, 3494 (1995)
  20. Grasso Luigi, Huang Minxue, Sullivan Christine D., Messler Carol J., Kiser Matt B., Dragwa Carl R., Holroyd Kenneth J., Renauld Jean-Christophe, Levitt Roy C., Nicolaides Nicholas C., Molecular Analysis of Human Interleukin-9 Receptor Transcripts in Peripheral Blood Mononuclear Cells : IDENTIFICATION OF A SPLICE VARIANT ENCODING FOR A NONFUNCTIONAL CELL SURFACE RECEPTOR, 10.1074/jbc.273.37.24016
  21. Gerhartz Claudia, Heesel Birgit, Sasse Jürgen, Hemmann Ulrike, Landgraf Christiane, Schneider-Mergener Jens, Horn Friedemann, Heinrich Peter C., Graeve Lutz, Differential Activation of Acute Phase Response Factor/STAT3 and STAT1 via the Cytoplasmic Domain of the Interleukin 6 Signal Transducer gp130 : I. DEFINITION OF A NOVEL PHOSPHOTYROSINE MOTIF MEDIATING STAT1 ACTIVATION, 10.1074/jbc.271.22.12991
  22. Hemmann Ulrike, Gerhartz Claudia, Heesel Birgit, Sasse Jürgen, Kurapkat Günther, Grötzinger Joachim, Wollmer Axel, Zhong Zhong, Darnell James E., Graeve Lutz, Heinrich Peter C., Horn Friedemann, Differential Activation of Acute Phase Response Factor/Stat3 and Stat1 via the Cytoplasmic Domain of the Interleukin 6 Signal Transducer gp130 : II. Src HOMOLOGY SH2 DOMAINS DEFINE THE SPECIFICITY OF STAT FACTOR ACTIVATION, 10.1074/jbc.271.22.12999
  23. Renauld, Oncogene, 9, 1327 (1994)
  24. Damen, EMBO J., 14, 5557 (1995)
  25. Renauld J. C., Druez C., Kermouni A., Houssiau F., Uyttenhove C., Van Roost E., Van Snick J., Expression cloning of the murine and human interleukin 9 receptor cDNAs., 10.1073/pnas.89.12.5690
  26. Demoulin, Eur. Cytokine Netw., 10, 49 (1999)
  27. Khan K. D., Shuai K., Lindwall G., Maher S. E., Darnell J. E., Bothwell A. L., Induction of the Ly-6A/E gene by interferon alpha/beta and gamma requires a DNA element to which a tyrosine-phosphorylated 91-kDa protein binds., 10.1073/pnas.90.14.6806
  28. Mui, EMBO J., 15, 2425 (1996)
  29. Berchtold Susanne, Moriggl Richard, Gouilleux Fabrice, Silvennoinen Olli, Beisenherz Christian, Pfitzner Edith, Wissler Manuela, Stöcklin Elisabeth, Groner Bernd, Cytokine Receptor-independent, Constitutively Active Variants of STAT5, 10.1074/jbc.272.48.30237
  30. Lilly, Oncogene, 7, 727 (1992)
  31. Buckley A. R., Rapid induction of pim-1 expression by prolactin and interleukin-2 in rat Nb2 lymphoma cells, 10.1210/en.136.12.5252
  32. Onishi Mayumi, Nosaka Tetsuya, Misawa Kazuhide, Mui Alice L.-F., Gorman Daniel, McMahon Martin, Miyajima Atsushi, Kitamura Toshio, Identification and Characterization of a Constitutively Active STAT5 Mutant That Promotes Cell Proliferation, 10.1128/mcb.18.7.3871
  33. Takeda, J. Immunol., 161, 4652 (1998)
  34. Nicolaides N. C., Holroyd K. J., Ewart S. L., Eleff S. M., Kiser M. B., Dragwa C. R., Sullivan C. D., Grasso L., Zhang L.-Y., Messler C. J., Zhou T., Kleeberger S. R., Buetow K. H., Levitt R. C., Interleukin 9: A candidate gene for asthma, 10.1073/pnas.94.24.13175
  35. Stöcklin Elisabeth, Wissler Manuela, Gouilleux Fabrice, Groner Bernd, Functional interactions between Stat5 and the glucocorticoid receptor, 10.1038/383726a0
  36. Zhang Zhixin, Jones Simon, Hagood James S., Fuentes Nelson L., Fuller Gerald M., STAT3 Acts as a Co-activator of Glucocorticoid Receptor Signaling, 10.1074/jbc.272.49.30607
  37. Temann Ulla-Angela, Geba Gregory P., Rankin John A., Flavell Richard A., Expression of Interleukin 9 in the Lungs of  Transgenic Mice Causes Airway Inflammation, Mast Cell Hyperplasia, and Bronchial Hyperresponsiveness, 10.1084/jem.188.7.1307
  38. McLane Michael P., Haczku Angela, van de Rijn Matthijs, Weiss Christine, Ferrante Veronica, MacDonald Dorothy, Renauld Jean-Christophe, Nicolaides Nicholas C., Holroyd Kenneth J., Levitt Roy C., Interleukin-9 Promotes Allergen-Induced Eosinophilic Inflammation and Airway Hyperresponsiveness in Transgenic Mice, 10.1165/ajrcmb.19.5.3457
  39. Renauld, Blood, 85, 1300 (1995)
  40. Vink Anne, Renauld Jean-Christophe, Warnier Guy, Van Snick Jacques, Interleukin-9 stimulatesin vitro growth of mouse thymic lymphomas, 10.1002/eji.1830230523
  41. Louahed, J. Immunol., 156, 3704 (1996)
Bibliographic reference Demoulin, Jean-Baptiste ; Van Roost, Emiel ; Stevens, Monique ; Groner, Bernd ; Renauld, Jean-Christophe. Distinct roles for STAT1, STAT3, and STAT5 in differentiation gene induction and apoptosis inhibition by interleukin-9. In: Journal of Biological Chemistry, Vol. 274, no. 36, p. 25855-25861 (1999)
Permanent URL http://hdl.handle.net/2078.1/8342