User menu

Accès à distance ? S'identifier sur le proxy UCLouvain

Interleukin-22 (IL-22) activates the JAK/STAT, ERK, JNK, and p38 MAP kinase pathways in a rat hepatoma cell line - Pathways that are shared with and distinct from IL-10

Primary tabs

Lejeune, Diane [UCL] Dumoutier, Laure [UCL] Constantinescu, Stefan N. [UCL] Kruijer, Wiebe Schuringa, Jan Jacob Renauld, Jean-Christophe [UCL]

IL (interleukin)-22 is an IL-10-related cytokine; its main biological activity known thus far is the induction of acute phase reactants in liver and pancreas. IL-22 signals through a receptor that is composed of two chains from the class II cytokine receptor family: IL-22R (also called ZcytoR11/CRF2-9) and IL-10Rbeta (CRF2-4), which is also involved in IL-10 signaling. In this report, we analyzed the signal transduction pathways activated in response to IL-22 in a rat hepatoma cell line, H4IIE. We found that IL-22 induces activation of JAK1 and Tyk2 but not JAK2, as well as phosphorylation of STAT1, STAT3, and STAT5 on tyrosine residues, extending the similarities between IL-22 and IL-10. However our results unraveled some differences between IL-22 and IL-10 signaling. Using antibodies specific for the phosphorylated form of MEK1/2, ERK1/2, p90RSK, JNK, and p38 kinase, we showed that IL-22 activates the three major MAPK,PK pathways. IL-22 also induced serine phosphorylation of STAT3 on Ser(727). This effect, which is not shared with IL-10, was only marginally affected by MEK1/2 inhibitors, indicating that other pathways might be involved. Finally, by overexpressing a STAT3 S727A mutant, we showed that serine phosphorylation is required to achieve maximum transactivation of a STAT responsive promoter upon IL-22 stimulation.

Document type Article de périodique (Journal article) – Article de recherche
Access type Accès restreint
Publication date 2002
Language Anglais
Journal information "Journal of Biological Chemistry" - Vol. 277, no. 37, p. 33676-82 (2002)
Peer reviewed yes
Publisher Amer Soc Biochemistry Molecular Biology Inc (Bethesda)
issn 0021-9258
e-issn 1083-351X
Publication status Publié
Affiliation UCL - MD/MIGE - Département de microbiologie, d'immunologie et de génétique
MESH Subject p38 Mitogen-Activated Protein Kinases ; Tumor Cells, Cultured ; Trans-Activators - metabolism ; TYK2 Kinase ; Signal Transduction - drug effects ; STAT5 Transcription Factor ; STAT3 Transcription Factor ; STAT1 Transcription Factor ; Rats ; Proto-Oncogene Proteins ; Proteins - metabolism ; Protein-Tyrosine Kinases - metabolism ; Phosphorylation ; Mitogen-Activated Protein Kinases - metabolism ; Milk Proteins ; Janus Kinase 2 ; JNK Mitogen-Activated Protein Kinases ; Interleukins - pharmacology ; Interleukin-10 - pharmacology ; Enzyme Activation - drug effects ; DNA-Binding Proteins - metabolism ; Carcinoma, Hepatocellular - enzymology ; Animals
Links
  1. Blumberg Hal, Conklin Darrell, Xu WenFeng, Grossmann Angelika, Brender Ty, Carollo Susan, Eagan Maribeth, Foster Don, Haldeman Betty A, Hammond Angie, Haugen Harald, Jelinek Laura, Kelly James D, Madden Karen, Maurer Mark F, Parrish-Novak Julia, Prunkard Donna, Sexson Shannon, Sprecher Cindy, Waggie Kim, West Jim, Whitmore Theodore E, Yao Lena, Kuechle Melanie K, Dale Beverly A, Chandrasekher Yasmin A, Interleukin 20, 10.1016/s0092-8674(01)00187-8
  2. Dumoutier L., Louahed J., Renauld J.-C., Cloning and Characterization of IL-10-Related T Cell-Derived Inducible Factor (IL-TIF), a Novel Cytokine Structurally Related to IL-10 and Inducible by IL-9, 10.4049/jimmunol.164.4.1814
  3. Sporn Michael, Vilcek Jan, Cytokine and Growth Factor Reviews to be published six times a year, 10.1016/s1359-6101(01)00026-0
  4. Finbloom, J. Immunol., 155, 1079 (1995)
  5. Kotenko Serguei V., Krause Christopher D., Izotova Lara S., Pollack Brian P., Wu Wei, Pestka Sidney, Identification and functional characterization of a second chain of the interleukin-10 receptor complex, 10.1093/emboj/16.19.5894
  6. Wehinger Jens, Gouilleux Fabrice, Groner Bernd, Finke Juergen, Mertelsmann Roland, Maria Weber-Nordt Renate, IL-10 induces DNA binding activity of three STAT proteins (Stat1, Stat3, and Stat5) and their distinct combinatorial assembly in the promoters of selected genes, 10.1016/0014-5793(96)00990-8
  7. Crawley James B., Williams Lynn M., Mander Tom, Brennan Fionula M., Foxwell Brian M. J., Interleukin-10 Stimulation of Phosphatidylinositol 3-Kinase and p70 S6 Kinase Is Required for the Proliferative but Not the Antiinflammatory Effects of the Cytokine, 10.1074/jbc.271.27.16357
  8. Sato, J. Immunol., 162, 3865 (1999)
  9. Geng Y., Gulbins E., Altman A., Lotz M., Monocyte deactivation by interleukin 10 via inhibition of tyrosine kinase activity and the Ras signaling pathway., 10.1073/pnas.91.18.8602
  10. Kohlhuber F, Rogers N C, Watling D, Feng J, Guschin D, Briscoe J, Witthuhn B A, Kotenko S V, Pestka S, Stark G R, Ihle J N, Kerr I M, A JAK1/JAK2 chimera can sustain alpha and gamma interferon responses., 10.1128/mcb.17.2.695
  11. Pellegrini S, John J, Shearer M, Kerr I M, Stark G R, Use of a selectable marker regulated by alpha interferon to obtain mutations in the signaling pathway., 10.1128/mcb.9.11.4605
  12. Moore Kevin W., de Waal Malefyt Rene, Coffman Robert L., O'Garra Anne, INTERLEUKIN-10AND THEINTERLEUKIN-10 RECEPTOR, 10.1146/annurev.immunol.19.1.683
  13. Dumoutier L., Lejeune D., Colau D., Renauld J.-C., Cloning and Characterization of IL-22 Binding Protein, a Natural Antagonist of IL-10-Related T Cell-Derived Inducible Factor/IL-22, 10.4049/jimmunol.166.12.7090
  14. Mizushima Seiichi, Nagata Shigekazu, pEF-BOS, a powerful mammalian expression vector, 10.1093/nar/18.17.5322
  15. SCHURINGA Jan-Jacob, JONK Luigi J. C., DOKTER Wim H. A., VELLENGA Edo, KRUIJER Wiebe, Interleukin-6-induced STAT3 transactivation and Ser727 phosphorylation involves Vav, Rac-1 and the kinase SEK-1/MKK-4 as signal transduction components, 10.1042/bj3470089
  16. Feng J, Witthuhn B A, Matsuda T, Kohlhuber F, Kerr I M, Ihle J N, Activation of Jak2 catalytic activity requires phosphorylation of Y1007 in the kinase activation loop., 10.1128/mcb.17.5.2497
  17. LEJEUNE Diane, DEMOULIN Jean-Baptiste, RENAULD Jean-Christophe, Interleukin 9 induces expression of three cytokine signal inhibitors: cytokine-inducible SH2-containing protein, suppressor of cytokine signalling (SOCS)-2 and SOCS-3, but only SOCS-3 overexpression suppresses interleukin 9 signalling, 10.1042/bj3530109
  18. Muller, EMBO J., 12, 4221 (1993)
  19. Decker Thomas, Kovarik Pavel, Serine phosphorylation of STATs, 10.1038/sj.onc.1203481
  20. Lim Cheh Peng, Cao Xinmin, Serine Phosphorylation and Negative Regulation of Stat3 by JNK, 10.1074/jbc.274.43.31055
  21. Schuringa Jan-Jacob, Schepers Hein, Vellenga Edo, Kruijer Wiebe, Ser727-dependent transcriptional activation by association of p300 with STAT3 upon IL-6 stimulation, 10.1016/s0014-5793(01)02354-7
  22. Dumoutier L., Leemans C., Lejeune D., Kotenko S. V., Renauld J.-C., Cutting Edge: STAT Activation By IL-19, IL-20 and mda-7 Through IL-20 Receptor Complexes of Two Types, 10.4049/jimmunol.167.7.3545
  23. Baumann Heinz, Gauldie Jack, The acute phase response, 10.1016/0167-5699(94)90137-6
  24. Dumoutier, Eur. Cytokine Netw., 13, 5 (2002)
  25. Wegenka U M, Lütticken C, Buschmann J, Yuan J, Lottspeich F, Müller-Esterl W, Schindler C, Roeb E, Heinrich P C, Horn F, The interleukin-6-activated acute-phase response factor is antigenically and functionally related to members of the signal transducer and activator of transcription (STAT) family., 10.1128/mcb.14.5.3186
  26. Seidel H. M., Milocco L. H., Lamb P., Darnell J. E., Stein R. B., Rosen J., Spacing of palindromic half sites as a determinant of selective STAT (signal transducers and activators of transcription) DNA binding and transcriptional activity., 10.1073/pnas.92.7.3041
  27. Hirano Toshio, Interleukin 6 and its Receptor: Ten Years Later, 10.3109/08830189809042997
  28. Fukada Toshiyuki, Hibi Masahiko, Yamanaka Yojiro, Takahashi-Tezuka Mariko, Fujitani Yoshio, Yamaguchi Takuya, Nakajima Koichi, Hirano Toshio, Two Signals Are Necessary for Cell Proliferation Induced by a Cytokine Receptor gp130: Involvement of STAT3 in Anti-Apoptosis, 10.1016/s1074-7613(00)80501-4
  29. Bode J.G., Ludwig S., Freitas C.A. Correia, Schaper F., Ruhl M., Melmed S., Heinrich P.C., Häussinger D., The MKK6/p38 Mitogen-Activated Protein Kinase Pathway Is Capable of Inducing SOCS3 Gene Expression and Inhibits IL-6-Induced Transcription, 10.1515/bc.2001.178
  30. Yoo Joo-Yeon, Wang Wenlan, Desiderio Stephen, Nathans Daniel, Synergistic Activity of STAT3 and c-Jun at a Specific Array of DNA Elements in the α2-Macroglobulin Promoter, 10.1074/jbc.m009935200
  31. Schuringa Jan-Jacob, Dekker Lodewijk V., Vellenga Edo, Kruijer Wiebe, Sequential Activation of Rac-1, SEK-1/MKK-4, and Protein Kinase Cδ Is Required for Interleukin-6-induced STAT3 Ser-727 Phosphorylation and Transactivation, 10.1074/jbc.m009821200
  32. Ng Julian, Cantrell Doreen, STAT3 Is a Serine Kinase Target in T Lymphocytes : INTERLEUKIN 2 AND T CELL ANTIGEN RECEPTOR SIGNALS CONVERGE UPON SERINE 727, 10.1074/jbc.272.39.24542
  33. Lim Cheh Peng, Cao Xinmin, Regulation of Stat3 Activation by MEK Kinase 1, 10.1074/jbc.m007592200
  34. Fickenscher Helmut, Hör Simon, Küpers Heide, Knappe Andrea, Wittmann Sabine, Sticht Heinrich, The interleukin-10 family of cytokines, 10.1016/s1471-4906(01)02149-4
  35. Goh K. C., p38 MAP kinase is required for STAT1 serine phosphorylation and transcriptional activation induced by interferons, 10.1093/emboj/18.20.5601
  36. Abe Koji, Hirai Manabu, Mizuno Katsunori, Higashi Natsuko, Sekimoto Toshihiro, Miki Tokuhiko, Hirano Toshio, Nakajima Koichi, The YXXQ motif in gp 130 is crucial for STAT3 phosphorylation at Ser727 through an H7-sensitive kinase pathway, 10.1038/sj.onc.1204461
  37. Aggarwal Sudeepta, Xie Ming-Hong, Maruoka Miko, Foster Jessica, Gurney Austin L., Acinar Cells of the Pancreas Are a Target of Interleukin-22, 10.1089/107999001317205178
  38. Dumoutier L., Van Roost E., Colau D., Renauld J.-C., Human interleukin-10-related T cell-derived inducible factor: Molecular cloning and functional characterization as an hepatocyte-stimulating factor, 10.1073/pnas.170291697
  39. Xie Ming-Hong, Aggarwal Sudeepta, Ho Wei-Hsien, Foster Jessica, Zhang Zemin, Stinson Jeremy, Wood William I., Goddard Audrey D., Gurney Austin L., Interleukin (IL)-22, a Novel Human Cytokine That Signals through the Interferon Receptor-related Proteins CRF2–4 and IL-22R, 10.1074/jbc.m005304200
  40. Kotenko Sergei V., Izotova Lara S., Mirochnitchenko Olga V., Esterova Elena, Dickensheets Harold, Donnelly Raymond P., Pestka Sidney, Identification of the Functional Interleukin-22 (IL-22) Receptor Complex : THE IL-10R2 CHAIN (IL-10Rβ) IS A COMMON CHAIN OF BOTH THE IL-10 AND IL-22 (IL-10-RELATED T CELL-DERIVED INDUCIBLE FACTOR, IL-TIF) RECEPTOR COMPLEXES, 10.1074/jbc.m007837200
  41. Kotenko Sergei V, Pestka Sidney, Jak-Stat signal transduction pathway through the eyes of cytokine class II receptor complexes, 10.1038/sj.onc.1203524
Bibliographic reference Lejeune, Diane ; Dumoutier, Laure ; Constantinescu, Stefan N. ; Kruijer, Wiebe ; Schuringa, Jan Jacob ; et. al. Interleukin-22 (IL-22) activates the JAK/STAT, ERK, JNK, and p38 MAP kinase pathways in a rat hepatoma cell line - Pathways that are shared with and distinct from IL-10. In: Journal of Biological Chemistry, Vol. 277, no. 37, p. 33676-82 (2002)
Permanent URL http://hdl.handle.net/2078.1/41691