Principles of interleukin (IL)-6-type cytokine signalling and its regulation

Biochemical Journal

Volumn 374, Issue 1, 2003, Pages 1-20

  Heinrich, Peter C ^a   Behrmann, Iris ^a   Haan, Serge ^a   Hermanns, Heike M ^a   Müller Newen, Gerhard ^a   Schaper, Fred ^a  

^a UNIVERSITY HOSPITAL RWTH AACHEN   (Germany)

Author keywords

Cytokine signalling; Glycoprotein 130 (gp 130) interleukin 6 (IL 6); Janus kinase (JAK), mitogen activated protein kinase (MAPK); Signal transducer and activator of transcription (STAT)

Indexed keywords

BIOCHEMISTRY; DISEASE CONTROL; ENZYME INHIBITION; GROWTH KINETICS; IMMUNOLOGY; NEUROLOGY;

PROTEIN INHIBITORS;

ENZYME KINETICS;

CARDIOTROPHIN 1; CARDIOTROPHIN LIKE CYTOKINE; CILIARY NEUROTROPHIC FACTOR; CYTOKINE; GLYCOPROTEIN GP 130; INTERLEUKIN 11; INTERLEUKIN 6; JANUS KINASE; LEUKEMIA INHIBITORY FACTOR; LEUKEMIA INHIBITORY FACTOR RECEPTOR; MITOGEN ACTIVATED PROTEIN KINASE; ONCOSTATIN M; PROTEIN INHIBITOR; PROTEIN INHIBITOR OF ACTIVATED STAT; PROTEIN TYROSINE PHOSPHATASE; STAT PROTEIN; SUPPRESSOR OF CYTOKINE SIGNALING; UNCLASSIFIED DRUG;

ACUTE PHASE RESPONSE; CANCER; CYTOKINE PRODUCTION; CYTOKINE RELEASE; EMBRYO DEVELOPMENT; ENTERITIS; ENZYME REGULATION; FERTILITY; HEMATOPOIESIS; HUMAN; IMMUNE RESPONSE; INFECTION; INFLAMMATION; INHIBITION KINETICS; INJURY; LIVER REGENERATION; MEDIATOR RELEASE; MOLECULAR MECHANICS; MULTIPLE MYELOMA; MULTIPLE SCLEROSIS; NERVE REGENERATION; OSTEOPOROSIS; PRIORITY JOURNAL; PROSTATE CANCER; PROTEIN CROSS LINKING; RECEPTOR UPREGULATION; REGULATORY MECHANISM; REVIEW; RHEUMATOID ARTHRITIS; SIGNAL TRANSDUCTION;

ANIMALS; CYTOKINES; HUMANS; INFECTION; INTERLEUKIN-6; MODELS, MOLECULAR; PHOSPHORYLATION; PROTEIN CONFORMATION; PROTEIN STRUCTURE, SECONDARY; RECEPTORS, INTERLEUKIN-6; SIGNAL TRANSDUCTION; WOUNDS AND INJURIES;

JANUS;

EID: 0041677606     PISSN: 02646021     EISSN: None     Source Type: Journal    
DOI: 10.1042/BJ20030407     Document Type: Review

References (260)

1. Levy, D. E. and Darnell, Jr, J. E. (2002) STATs: transcriptional control and biological impact. Nat Rev. Mol. Cell Biol. 3, 656-662
2. Brivanlou, A. H. and Darnell, Jr, J. E. (2002) Signal transduction and the control of gene expression. Science (Washington, D.C.) 295, 813-818
3. O'Shea, J. J., Gadina, M. and Schreiber, R. D. (2002) Cytokine signaling in 2002: new surprises in the Jak/Stat pathway. Cell (Cambridge, Mass.) 109 (suppl), S121-S131
4. Heinrich, P. C., Behrmann, I., Müller-Newen, G., Schaper, F. and Graeve, L. (1998) IL-6-type cytokine signalling through the gp130/JAK/STAT pathway. Biochem J. 334, 297-314
5. Robledo, O., Fourcin, M., Chevalier, S., Guillet, C., Auguste, P., Pouplard-Barthelaix, A., Pennica, D. and Gascan, H. (1997) Signaling of the cardiotrophin-1 receptor. Evidence for a third receptor component. J. Biol. Chem. 272, 4855-4863
6. Senaldi, G., Varnum, B. C., Sarmiento, U., Starnes, C., Lile, J., Scully, S., Guo, J., Elliott, G., McNinch, J., Shaklee, C. L. et al. (1999) Novel neurotrophin-1/B cell-stimulating factor-3: a cytokine of the IL-6 family. Proc. Natl. Acad. Sci. U.S.A. 96, 11458-11463
7. Müller-Newen, G., Küster, A., Hemmann, U., Keul, R., Horsten, U., Martens, A., Graeve, L., Wijdenes, J. and Heinrich, P. C. (1998) Soluble interleukin-6 receptor potentiates the antagonistic activity of soluble gp130 on interleukin-6 responses. J. Immunol. 161, 6347-6355
8. 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
9. Koshelnick, Y., Ehart, M., Hufnagl, P., Heinrich, P. C. and Binder, B. R. (1997) Urokinase receptor is associated with the components of the JAK1/STAT1 signaling pathway and leads to activation of this pathway upon receptor clustering in the human kidney epithelial tumor cell line TCL-598. J. Biol. Chem. 272, 28563-28567
10. Podar, K., Tai, Y. T., Cole, C. E., Hideshima, T., Sattler, M., Hamblin, A., Mitsiades, N., Schlossman, R. L., Davies, F. E., Morgan, G. J., Munshi, N. C., Chauhan, D. and Anderson, K. C. (2002) Essential role of caveolae in IL-6- and IGF-I- triggered Akt-1- mediated survival of multiple myeloma cells. J. Biol. Chem. 278, 5794-5801
11. Sehgal, P. B., Guo, G. G., Shah, M., Kumar, V. and Patel, K. (2002) Cytokine signaling: STATS in plasma membrane rafts. J. Biol. Chem. 277, 12067-12074
12. Elson, G. C. A., Lelièvre, E., Guillet, C., Chevalier, S., Plun-Favreau, H., Roger, J., Suard, I., Benoit de Coignac, A., Delneste, Y., Bonnefoy, J.-F. et al. (2000) CLF associates with CLC to form a functional heteromeric ligand for the CNTF receptor complex. Nat. Neurosci. 3, 867-872
13. Plun-Favreau, H., Elson, G., Chabbert, M., Roger, J., deLapeyriere, O., Lelievre, E., Guillet, C., Hermann, J., Gauchat, J. F., Gascan, H. and Chevalier, S. (2001) The ciliary neurotrophic factor receptor α component induces the secretion of and is required for functional responses to cardiotrophin-like cytokine. EMBO J. 20, 1692-1703
14. Moore, P. S., Boshoff, C., Weiss, R. A. and Chang, Y. (1996) Molecular mimicry of human cytokine and cytokine response pathway genes by KSHV. Science (Washington, D.C.) 274, 1739-1744
15. Kaleeba, J. A., Bergquam, E. P. and Wong, S. W. (1999) A rhesus macaque rhadinovirus related to Kaposi's sarcoma-associated herpesvirus/human herpesvirus 8 encodes a functional homologue of interleukin-6. J. Virol. 73, 6177-6181
16. Hoischen, S. H., Vollmer, P., Marz, P., Ozbek, S., Gotze, K. S., Peschel, C., Jostock, T., Geib, T., Mullberg, J., Mechtersheimer, S. et al. (2000) Human herpes virus 8 interleukin-6 homologue triggers gp130 on neuronal and hematopoietic cells. Eur. J. Biochem. 267, 3604-3612
17. Bravo, J. and Heath, J. K. (2000) Receptor recognition by gp130 cytokines. EMBO J. 19, 2399-2411
18. Deller, M. C., Hudson, K. R., Ikemizu, S., Bravo, J., Jones, E. Y. and Heath, J. K. (2000) Crystal structure and functional dissection of the cytostatic cytokine oncostatin M. Structure Fold. Des. 8, 863-874
19. Owczarek, C. M., Zhang, Y., Layton, M. J., Metcalf, D., Roberts, B. and Nicola, N. A. (1997) The unusual species cross-reactivity of the leukemia inhibitory factor receptor α-chain is determined primarily by the immunoglobulin-like domain. J. Biol. Chem. 272, 23976-23985
20. Hammacher, A., Richardson, R. T., Layton, J. E., Smith, D. K., Angus, L. J. L., Hilton, D. J., Nicola, N. A., Wijdenes, J. and Simpson, R. J. (1998) The immunoglobulin-like module of gp130 is required for signaling by interleukin-6 but not by leukemia inhibitory factor. J. Biol. Chem. 273, 22701-22707
21. Kurth, I., Horsten, U., Pflanz, S., Dahmen, H., Küster, A., Grötzinger, J., Heinrich, P. C. and Müller-Newen, G. (1999) Activation of the signal transducer gp130 by both interleukin-6 and interleukin-11 requires two distinct binding epitopes. J. Immunol. 162, 1480-1487
22. Timmermann, A., Pflanz, S., Grötzinger, J., Küster, A., Kurth, I., Pitard, V., Heinrich, P. C. and Müller-Newen, G. (2000) Different epitopes are required for gp130 activation by interleukin-6, oncostatin M and leukemia inhibitory factor. FEBS Lett. 468, 120-124
23. Pflanz, S., Kurth, I., Grötzinger, J., Heinrich, P. C. and Müller-Newen, G. (2000) Two different epitopes of the signal transducer gp130 sequentially cooperate on IL-6-induced receptor activation. J. Immunol. 165, 7042-7049
24. Chow, D., He, X., Snow, A. L., Rose-John, S. and Garcia, K. C. (2001) Structure of an extracellular gp130 cytokine receptor complex. Science (Washington, D.C.) 291, 2150-2155
25. Varghese, J. N., Moritz, R. L., Lou, M. Z., Van Donkelaar, A., Ji, H., Ivancic, N., Branson, K. M., Hall, N. E. and Simpson, R. J. (2002) Structure of the extracellular domains of the human interleukin-6 receptor α-chain Proc. Natl. Acad. Sci. U.S.A. 99, 15959-15964
26. Dittrich, E., Renfrew Haft, C., 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
27. Thiel, S., Behrmann, I., Timmermann, A., Dahmen, H., Müller-Newen, G., Schaper, F., Tavernier, J., Pitard, V., Heinrich, P. C. and Graeve, L. (1999) Identification of a Leu-Ile internalization motif within the cytoplasmic domain of the leukaemia inhibitory factor receptor. Biochem. J. 339, 15-19
28. Thiel, S., Dahmen, H., Martens, A., Müller-Newen, G., Schaper, F., Heinrich, P. C. and Graeve, L. (1998) Constitutive internalization and association with adaptor protein-2 of the interleukin-6 signal transducer gp130. FEBS Lett. 441, 231-234
29. Gibson, R. M., Schiemann, W. P., Prichard, L. B., Reno, J. M., Ericsson, L. H. and Nathanson, N. M. (2000) Phosphorylation of human gp130 at Ser-782 adjacent to the di-leucine internalization motif. Effects on expression and signaling. J. Biol. Chem. 275, 22574-22582
30. Wang, Y. and Fuller, G. M. (1994) Phosphorylation and internalization of gp130 occur after IL-6 activation of Jak2 kinase in hepatocytes. Mol. Biol. Cell 5, 819-828
31. Blanchard, F., Duplomb, L., Wang, Y., Robtedo, O., Kinzie, E., Pitard, V., Godard, A., Jacques, Y. and Baumann, H. (2000) Stimulation of leukemia inhibitory factor receptor degradation by extracellular signal-regulated kinase. J. Biol. Chem. 275, 28793-28801
32. Blanchard, F., Wang, Y., Kinzie, E., Duplomb, L., Godard, A. and Baumann, H. (2001) Oncostatin M regulates the synthesis and turnover of gp130, leukemia inhibitory tactor receptor α, and oncostatin M receptor β by distinct mechanisms. J. Biol. Chem. 276, 47038-47045
33. Strobl, B., Arulampalam, V., Is'harc, H., Newman, S. J., Schlaak, J. F., Watling, D., Costa-Pereira, A. P., Schaper, F., Behrmann, I., Sheehan, K. C. et al. (2001) A completely foreign receptor can mediate an interferon-γ-like response. EMBO J. 20, 5431-5442
34. Mitani, Y., Takaoka, A., Kim, S. H., Kato, Y., Yokochi, T., Tanaka, N. and Taniguchi, T. (2001) Cross talk of the interferon-α/β signalling complex with gp130 for effective interleukin-6 signalling. Genes Cells 6, 631-640
35. Qiu, Y., Ravi, L. and Kung, H.-J. (1998) Requirement of ErbB2 for signalling by interleukin-6 in prostate carcinoma cells. Nature (London) 393, 83-85
36. Kurth, I., Horsten, U., Pflanz, S., Timmermann, A., Küster, A., Dahmen, H., Tacken, I., Heinrich, P. C. and Müller-Newen, G. (2000) Importance of the membrane-proximal extracellular domains for activation of the signal transducer gp130. J. Immunol. 164, 273-282
37. Hammacher, A., Wijdenes, J., Hilton, D. J., Nicola, N. A., Simpson, R. J. and Layton, J. E. (2000) Ligand-specific utilization of the extracellular membrane-proximal region of the gp130-related signalling receptors. Biochem. J. 345, 25-32
38. Timmermann, A., Küster, A., Kurth, I., Heinrich, P. C. and Müller-Newen, G. (2002) A functional role of the membrane-proximal extracellular domains of the signal transducer gp130 in heterodimerization with the leukemia inhibitory factor receptor. Eur. J. Biochem. 269, 2716-2726
39. Autissier, P., De Vos, J., Liautard, J., Tupitsyn, N., Jacquet, C., Chavdia, N., Klein, B., Brochier, J. and Galliard, J. P. (1998) Dimerization and activation of the common transducing chain (gp130) of the cytokines of the IL-6 family by mAb. Int. Immunol. 10, 1881-1889
40. Müller-Newen, G., Küster, A., Wijdenes, J., Schaper, F. and Heinrich, P. C. (2000) Studies on the IL-6-type cytokine signal transducer gp130 reveal a novel mechanism of receptor activation by monoclonal antibodies. J. Biol. Chem. 275, 4579-4586
41. Livnah, O., Stura, E. A., Middleton, S. A., Johnson, D. L., Jolliffe, L. K. and Wilson, I. A. (1999) Crystallographic evidence for preformed dimers of erythropoietin receptor before ligand activation. Science (Washington, D.C.) 283, 987-990
42. Chan, F. K., Chun, H. J., Zheng, L., Siegel, R. M., Bui, K. L. and Lenardo, M. J. (2000) A domain in TNF receptors that mediates ligand-independent receptor assembly and signaling. Science (Washington, D.C.) 288, 2351-2354
43. Ballinger, M. D. and Wells, J. A. (1998) Will any dimer do? Nat. Struct. Biol. 5, 938-940
44. Jiang, G. and Hunter, T. (1999) Receptor signaling: When dimerization is not enough. Curr. Biol. 9, R568-R571
45. Greiser, J. S., Stross, C., Heinrich, P. C., Behrmann, I. and Hermanns, H. M. (2002) Orientational constraints of the gp130 intracellular juxtamembrane domain for signaling. J. Biol. Chem. 277, 26959-26965
46. Constantinescu, S. N., Huang, L. J., Nam, H. and Lodish, H. F. (2001) The erythropoietin receptor cytosolic juxtamembrane domain contains an essential, precisely oriented, hydrophobic motif. Mol. Cell 7, 377-385
47. Lütticken, C., Wegenka, U. M., Yuan, J., Buschmann, J., Schindler, C., Ziemiecki, A., Harpur A. G., Wilks, A. F., Yasukawa, K., Taga, T. et al. (1994) Association of transcription factor APRF and protein kinase JAK1 with the interleukin-6 signal transducer gp130. Science (Washington, D.C.) 263, 89-92
48. Stahl, N., Boulton, T. G., Farruggella, T., Ip, N. Y., Davis, S., Witthuhn, B. A., Quelle, F. W., Silvennoinen, O., Barbieri, G., Pellegrini, S. et al. (1994) Association and activation of Jak-Tyk kinases by CNTF-LIF-OSM-IL-6β receptor components. Science (Washington, D.C.) 263, 92-95
49. Radtke, S., Hermanns, H. M., Haan, C., Schmitz-Van De Leur, H., Gascan, H., Heinrich, P. C. and Behrmann, I. (2002) Novel role of Janus kinase 1 in the regulation of oncostatin M receptor surface expression. J. Biol. Chem. 277, 11297-11305
50. Hermanns, H. M., Radtke, S., Haan, C., Schmitz-Van de Leur, H., Tavernier, J., Heinrich, P. C. and Behrmann, I. (1999) Contributions of leukemia inhibitory factor receptor and oncostatin M receptor to signal transduction in heterodimeric complexes with glycoprotein 130. J. Immunol. 163, 6651-6658
51. Guschin, D., Rogers, N., Briscoe, J., Witthuhn, B., Walling, D., Horn, F., Pellegrini, S., Yasukawa, K., Heinrich, P., Stark, G. R. and Kerr, I. M. (1995) A major role for the protein tyrosine kinase JAK1 in the JAK/STAT signal transduction pathway in response to interleukin-6. EMBO J. 14, 1421-1429
52. Rodig, S. J., Meraz, M. A., White, J. M., Lampe, P. A., Riley, J. K., Arthur, C. D., King, K. L., Sheehan, K. C., Yin, L., Pennica, D., Johnson, E. M., Jr, and Schreiber, R. D. (1998) Disruption of the Jak1 gene demonstrates obligatory and nonredundant roles of the Jaks in cytokine-induced biologic responses. Cell (Cambridge, Mass.) 93, 373-383
53. Murakami, M., Narazaki, M., Hibi, M., Yawata, H., Yasukawa, K., Hamaguchi, M., Taga, T. and Kishimoto, T. (1991) Critical cytoplasmic region of the interleukin 6 signal transducer gp130 is conserved in the cytokine receptor family. Proc. Natl. Acad. Sci. U.S.A. 88, 11349-11353
54. 666 → Ala) in the interbox1/ 2 region of the interleukin-6 signal transducer gp136 abrogates binding of JAK1, and dominantly impairs signal transduction. Biochem. J. 349, 261-266
55. Haan, C., Heinrich, P. C. and Behrmann, I. (2002) Structural requirements of the interleukin-6 signal transducer gp130 for its interaction with Janus kinase 1: the receptor is crucial for kinase activation. Biochem. J. 361, 105-111
56. Lai, C. F., Ripperger, J., Morella, K. K., Wang, Y., Gearing, D. P., Fey, G. H. and Baumann, H. (1995) Separate signaling mechanisms are involved in the control of STAT protein activation and gene regulation via the intedeukin 6 response element by the box 3 motif of gp130 J. Biol. Chem. 270, 14847-14850
57. Tanner, J. W., Chen, W., Young, R. L., Longmore, G. D. and Shaw, A. S. (1995) The conserved box 1 motif of cytokine receptors is required for association with JAK kinases. J. Biol. Chem. 270, 6523-6530
58. Kishimoto, T., Akira, S., Narazaki, M. and Taga, T. (1995) Interleukin-6 family of cytokines and gp130. Blood 86, 1243-1254
59. Huang, L. J., Constantinescu, S. N. and Lodish, H. F. (2001) The N-terminal domain of Janus kinase 2 is required for Golgi processing and cell surface expression of erythropoietin receptor. Mol. Cell 8, 1327-1338
60. Pearson, M. A., Reczek, D., Bretscher, A. and Karplus, P. A. (2000) Structure of the ERM protein moesin reveals the FERM domain fold masked by an extended actin binding tail domain. Cell (Cambridge, Mass.) 101, 259-270
61. Hamada, K., Shimizu, T., Matsui, T., Tsukita, S. and Hakoshima, T. (2000) Structural basis of the membrane-targeting and unmasking mechanisms of the radixin FERM domain. EMBO J. 19, 4449-4462
62. Han, B. G., Nunomura, W., Takakuwa, Y., Mohandas, N. and Jap, B. K. (2000) Protein 4.1R core domain structure and insights into regulation of cytoskeletal organization. Nat. Struct. Biol. 7, 871-875
63. Haan, C., Is'harc, H., Hermanns, H. M., Schmitz-Van De Leur, H., Kerr, I. M., Heinrich, P. C., Grötzinger, J. and Behrmann, I. (2001) Mapping of a region within the N-terminus of Jak1 involved in cytokine receptor interaction. J. Biol. Chem. 276, 37451-37458
64. Zhou, Y. J., Chen, M., Cusack, N. A., Kimmel, L. H., Magnuson, K. S., Boyd, J. G., Lin, W., Roberts, J. L., Lengi, A., Buckley, R. H. et al. (2001) Unexpected effects of FERM domain mutations on catalytic activity of Jak3: structural implication for Janus kinases. Mol. Cell 8, 959-969
65. Schaeffer, M., Schneiderbauer, M., Weidler, S., Tavares, R., Warmuth, M., de Vos, G. and Hallek, M. (2001) Signaling through a novel domain of gp130 mediates cell proliferation and activation of Hck and Erk kinases. Mol. Cell. Biol. 21, 8068-8081
66. De Falco, G., Neri, L. M., Falco, M. D., Bellan, C., Yu, Z., Luca, A. D., Leoncini, L. and Giordano, A. (2002) Cdk9, a member of the cdc2-like family of kinases, binds to gp130, the receptor of the IL-6 family of cytokines. Oncogene 21, 7464-7470
67. Novotny-Diermayr, V., Zhang, T., Gu, L. and Cao, X. (2002) Protein kinase Cδ associates with the interleukin-6 receptor subunit glycoprotein (gp) 130 via Stat3 and enhances STAT3-gp130 interaction. J. Biol. Chem. 277, 49134-49142
68. Gauzzi, M. C., Barbieri, G., Richter, M. F., Uze, G., Ling, L., Fellous, M. and Pellegrini, S. (1997) The N-terminal region of Tyk2 sustains the level of interferon α receptor 1, a component of the interferon α/β receptor. Proc. Natl. Acad. Sci. U.S.A. 94, 11839-11844
69. Ragimbeau, J., Dondi, E., Alcover, A., Eid, P., Uze, G. and Peltegrini, S. (2083) The tyrosine kinase Tyk2 controls IFNAR1 cell surface expression. EMBO J. 22, 537-547
70. Vinkemeier, U., Moarefi, I., Darnell, Jr, J. E. and Kuriyan, J. (1998) Structure of the N-terminal protein interaction domain of STAT4. Science (Washington, D.C.) 279, 1048-1052
71. Chen, X., Vinkemeier, U., Zhao, Y., Jeruzalmi, D., Darnell, Jr, J. E. and Kuriyan, J. (1998) Crystal structure of a tyrosine phosphorylated STAT-1 dimer bound to DNA. Cell (Cambridge, Mass.) 93, 827-839
72. Decker, S., Groner, B. and Müller, C. W. (1998) Three-dimensional structure of the Stat3β homodimer bound to DNA. Nature (London) 394, 145-151
73. Fu, X. Y. and Zhang, J. J. (1993) Transcription factor p91 interacts with the epidermal growth factor receptor and mediates activation of the c-fos gene promoter. Cell (Cambridge, Mass.) 74, 1135-1145
74. Greenlund, A. C., Farrar, M. A., Viviano, B. L. and Schreiber, R. D. (1994) Ligand-induced IFN gamma receptor tyrosine phosphorylation couples the receptor to its signal transduction system (p91). EMBO J. 13, 1591-1608
75. Stancato, L. F., David, M., Carter-Su, C., Larner, A. C. and Pratt, W. B. (1996) Preassociation of STAT1 with STAT2 and STAT3 in separate signalling complexes prior to cytokine stimulation. J. Biol. Chem. 271, 4134-4137
76. Novak, U., Ji, H., Kanagasundaram, V., Simpson, R. and Paradiso, L. (1998) STAT3 forms stable homodimers in the presence of divalent cations prior to activation. Biochem. Biophys. Res. Commun. 247, 558-563
77. Ndubuisi, M. I., Guo, G. G., Fried, V. A., Etlinger, J. D. and Sehgal, P. B. (1999) Cellular physiology of STAT3: Where's the cytoplasmic monomer? J. Biol. Chem. 274, 25499-25509
78. Haan, S., Kortylewski, M., Behrmann, I., Müller-Esterl, W., Heinrich, P. C. and Schaper, F. (2000) Cytoplasmic STAT proteins associate prior to activation. Biochem. J. 345, 417-421
79. Shah, M., Patel, K., Fried, V. A. and Sehgal, P. B. (2002) Interactions of STAT3 with caveolin-1 and heat shock protein 90 in plasma membrane raft and cytosolic complexes. Preservation of cytokine signaling during fever. J. Biol. Chem. 277, 45662-45669
80. Fujitani, Y., Hibi, M., Fukada, T., Takahashi-Tezuka, M., Yoshida, H., Yamaguchi, T., Sugiyama, K., Yamanaka, Y., Nakajima, K. and Hirano, T. (1997) An alternative pathway for STAT activation that is mediated by the direct interaction between JAK and STAT. Oncogene 14, 751-761
81. 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. Science (Washington, D.C.) 267, 1349-1353
82. Heim, M. H., Kerr, I. M., Stark, G. R. and Darnell, Jr, J. E. (1995) Contribution of STAT SH2 groups to specific interferon signaling by the Jak-STAT pathway. Science (Washington, D.C.) 267, 1347-1349
83. Hemmann, U., Gerhartz, C., Heesel, B., Sasse, J., Kurapkat, G., Grötzinger, J., Wollmer, A., Zhong, Z., Darnell, Jr, J. E., Graeve, L. et al. (1996) 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. J. Biol. Chem. 271, 12999-13007
84. Gerhartz, C., Heesel, B., Sasse, J., Hemmann, U., Landgraf, C., Schneider-Mergener, J., Horn, F., Heinrich, P. C. and Graeve, L. (1996) Differential activation of acute phase response factor/STAT3 and STAT1 via the cytoplasmic domain of the interleukin-6 signal transducer gp130. 1. Definition of a novel phosphotyrosine motif mediating STAT1 activation. J. Biol. Chem. 271, 12991-12998
85. Kuropatwinski, K. K., De Imus, C., Gearing, D., Baumann, H. and Mosley, B. (1997) Influence of subunit combinations on signaling by receptors for oncostatin M, leukemia inhibitory factor, and interleukin-6. J. Biol. Chem. 272, 15135-15144
86. Tomida, M., Heike, T. and Yokota, T. (1999) Cytoplasmic domains of the leukemia inhibitory factor receptor required for STAT3 activation, differentiation, and growth arrest of myeloid leukemic cells. Blood 93, 1934-1941
87. Schmitz, J., Dahmen, H., Grimm, C., Gendo, C., Müller-Newen, G., Heinrich, P. C. and Schaper, F. (2000) The cytoplasmic tyrosine motifs in full-length gp130 have different roles in IL-6 signal transduction. J. Immunol. 164, 848-854
88. Shuai, K., Stark, G. R., Kerr, I. M. and Darnell, Jr, J. E. (1993) A single phosphotyrosine residue of Stat91 required for gene activation by interferon-γ. Science (Washington, D.C.) 261, 1744-1746
89. Kaptein, A., Paillard, V. and Saunders, M. (1996) Dominant negative stat3 mutant inhibits interleukin-6-induced Jak-STAT signal transduction J. Biol. Chem. 271, 5961-5964
90. Shuai, K., Horvath, C. M., Huang, L. H., Qureshi, S. A., Cowbum, D. and Darnell, Jr, J. E. (1994) Interferon activation of the transcription factor Stat91 involves dimerization through SH2-phosphotyrosyl peptide interactions. Cell (Cambridge, Mass.) 76, 821-828
91. Haan, S., Hemmann, U., Hassiepen, U., Schaper, F., Schneider-Mergener, J., Wollmer, A., Heinrich, P. C. and Grotzinger, J. (1999) Characterization and binding specificity of the monomeric STAT3-SH2 domain. J. Biol. Chem. 274, 1342-1348
92. Pfeffer, L. M., Mullersman, J. E., Pfeffer, S. R., Murti, A., Shi, W. and Yang, C. H. (1997) STAT3 as an adapter to couple phosphatidylinositol 3-kinase to the IFNAR1 chain of the type I interteron receptor. Science (Washington, D.C.) 276, 1418-1420
93. Uddin, S., Sassano, A., Deb, D. K., Verma, A., Majchrzak, B., Rahman, A., Malik, A. B., Fish, B. N. and Platanias, L. C. (2002) Protein kinase C-δ (PKC-δ) is activated by type I interterons and mediates phosphorylation of Stat1 on serine 727. J. Biol. Chem. 277, 14408-14416
94. Jain, N., Zhang, T., Kee, W. H., Li, W. and Cao, X. (1999) Protein kinase Cδ associates with and phosphorylates Stat3 in an interleukin-6-dependent manner. J. Biol. Chem. 274, 24392-24400
95. Schuringa, J. J., Dekker, L. V., Vellenga, E. and Kruijer, W. (2001) 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. J. Biol. Chem. 276, 27709-27715
96. Schuringa, J. J., Jonk, L. J., Dokter, W. H., Vellenga, E. and Kruijer, W. (2000) Interleukin-6-induced STAT3 transactivation and Ser727 phosphorylation involves Vav, Rat-1 and the kinase SEK-1/MKK-4 as signal transduction components. Biochem. J. 347, 89-96
97. Lim, C. P. and Cao, X. (2001) Regulation of Stat3 activation by MEK kinase 1. J. Biol. Chem. 276, 21004-21011
98. 727 through an H7-sensitive kinase pathway. Oncogene 20, 3464-3474
99. 2+ and CaMKII for Stat1 Ser-727 phosphorylation in response to IFN-γ. Proc. Natl. Acad. Sci. U.S.A. 99, 5971-5976
100. Haq, R., Halupa, A., Beattie, B. K., Mason, J. M., Zanke, B. W. and Barber, D. L. (2002) Regulation of erythropoietin-induced STAT serine phosphorylation by distinct mitogen-activated protein kinases. J. Biol. Chem. 277, 17359-17366
101. Beuvink, I., Hess, D., Flotow, H., Hofsteenge, J., Groner, B. and Hynes, N. E. (2000) Stat5a serine phosphorylation. Serine 779 is constitutively phosphorylated in the mammary gland, and serine 725 phosphorylation influences prolactin-stimulated in vitro DNA binding activity. J. Biol. Chem. 275, 10247-10255
102. Sanceau, J., Hiscott, J., Delattre, O. and Wietzerbin, J. (2000) IFN-β induces serine phosphorylation of Stat-1 in Ewing's sarcoma cells and mediates apoptosis via induction of IRF-1 and activation of caspase-7. Oncogene 19, 3372-3383
103. Lütticken, C., Coffer, P., Yuan, J., Schwartz, C., Caldenhoven, E., Schindler, C., Kruijer, W., Heinrich, P. C. and Horn, F. (1995) Interleukin-6-induced serine phosphorylation of transcription factor APRF: evidence for a role in interleukin-6 target gene induction. FEBS Lett. 360, 137-143
104. Boulton, T. G., Zhong, Z., Wen, Z., Darnell, Jr, J. E., Stahl, N. and Yancopoulos, G. D. (1995) STAT3 activation by cytokines utilizing gp130 and related transducers involves a secondary modification requiring an H7-sensitive kinase. Proc. Natl. Acad. Sci. U.S.A. 92, 6915-6919
105. Chung, J., Uchida, E., Grammer, T. C. and Blenis, J. (1997) STAT3 serine phosphorylation by ERK-dependent and -independent pathways negatively modulates its tyrosine phosphorylation. Mol. Cell. Biol. 17, 6508-6516
106. Abramovich, C., Yakobson, B., Chebath, J. and Revel, M. (1997) A protein-arginine methyltransferase binds to the intracytoplasmic domain of the IFNAR1 chain in the type I interferon receptor. EMBO J. 16, 260-266
107. Pollack, B. P., Kotenko, S. V., He, W., Izotova, L. S., Barnoski, B. L. and Pestka, S. (1999) The human homologue of the yeast proteins Skb1 and Hsl7p interacts with Jak kinases and contains protein methyltransferase activity. J. Biol. Chem. 274, 31531-31542
108. Mowen, K. A., Tang, J., Zhu, W., Schurter, B. T., Shuai, K., Herschman, H. R. and David, M. (2001) Arginine methylation of STAT1 modulates IFNα/β-induced transcription. Cell (Cambridge, Mass.) 104, 731-741
109. Sekimoto, T., Imamoto, N., Nakajima, K., Hirano, T. and Yoneda, Y. (1997) Extracellular signal-dependent nuclear import of Stat1 is mediated by nuclear pore-targeting complex formation with NPI-1, but not Rch1. EMBO J. 16, 7067-7077
110. McBride, K. M., McDonald, C. and Reich, N. C. (2000) Nuclear export signal located within the DNA-binding domain of the STAT1 transcription factor EMBO J. 19, 6196-6206
111. Begitt, A., Meyer, T., van Rossum, M. and Vinkemeier, U. (2000) Nucleocytoplasmic translocation of Stat1 is regulated by a leucine-rich export signal in the coiled-coil domain. Proc. Natl. Acad. Sci. U.S.A. 97, 10418-10423
112. Bromberg, J. F., Wrzeszczynska, M. H., Devgan, G., Zhao, Y., Pestell, R. G., Albanese, C. and Darnell, Jr, J. E. (1999) Stat3 as an oncogene. Cell (Cambridge, Mass.) 98, 295-303
113. Milocco, L. H., Haslam, J. A., Rosen, J. and Seidel, H. M. (1999) Design of conditionally active STATs: insights into STAT activation and gene regulatory function. Mol. Cell. Biol. 19, 2913-2920
114. Bild, A. H., Turkson, J. and Jove, R. (2002) Cytoplasmic transport of Stat3 by receptor-mediated endocytosis. BMBO J. 21, 3255-3263
115. Lillemeier, B. F., Köster, M. and Kerr, I. M. (2001) STAT1 from the cell membrane to the DNA. BMBO J. 20, 2508-2517
116. Spiekermann, K., Pau, M., Schwab, R., Schmieja, K., Franzrahe, S. and Hiddemann, W. (2002) Constitutive activation of STAT3 and STAT5 is induced by leukemic fusion proteins with protein tyrosine kinase activity and is sufficient for transformation of hematopoietic precursor cells. Exp. Hematol. 30, 262-271
117. Herrington, J., Rui, L., Lug, G., Yu-Lee, L. Y. and Carter-Su, C. (1999) A functional DNA binding domain is required for growth hormone-induced nuclear accumulation of Stat5B. J. Biol. Chem. 274, 5138-5145
118. McBride, K. M., Banninger, G., McDonald, C. and Reich, N. C. (2002) Regulated nuclear import of the STAT1 transcription factor by direct binding of importin-α. EMBO J. 21, 1754-1763
119. Meyer, T., Begitt, A., Lodige, I., van Rossum, M. and Vinkemeier, U. (2002) Constitutive and IFN-γ-induced nuclear import of STAT1 proceed through independent pathways. EMBO J. 21, 344-354
120. Melen, K., Kinnunen, L. and Julkunen, I. (2001) Arginine/lysine-rich structural element is involved in interferon-induced nuclear import of STATs. J. Biol. Chem. 276, 16447-16455
121. Fagerlund, R., Melen, K., Kinnunen, L. and Julkunen, I. (2002) Arginine/lysine-rich nuclear localization signals mediate interactions between dimeric STATs and importin α5. J. Biol. Chem. 277, 30072-30078
122. Mowen, K. and David, M. (2000) Regulation of STAT1 nuclear export by Jak1. Mol. Cell. Biol. 20, 7273-7281
123. Haspel, R. L. and Darnell, Jr, J. E. (1999) A nuclear protein tyrosine phosphatase is required for the inactivation of Stat1. Proc. Natl. Acad. Sci. U.S.A. 96, 10188-10193
124. Meyer, T., Gavenis, K. and Vinkemeier, U. (2002) Cell type-specific and tyrosine phosphorylation-independent nuclear presence of STAT1 and STAT3. Exp. Cell Res. 272, 45-55
125. Zeng, R., Aoki, Y., Yoshida, M., Arai, K. and Watanabe, S. (2002) Stat5B shuttles between cytoplasm and nucleus in a cytokine-dependent and -independent manner. J. Immunol. 168, 4567-4575
126. Kumar, A., Commane, M., Flickinger, T. W., Horvath, C. M. and Stark, G. B. (1997) Defective TNF-α-induced apoptosis in STAT1-null cells due to low constitutive levels of caspases. Science (Washington, D.C.) 278, 1630-1632
127. Chatterjee-Kishore, M., Wright, K. L., Ting, J. P. and Stark, G. R. (2000) How Stat1 mediates constitutive gene expression: a complex of unphosphorylated Stat1 and IRF1 supports transcription of the LMP2 gene. EMBO J. 19, 4111-4122
128. Andrews, R. P., Ericksen, M. B., Cunningham, C. M., Daines, M. O. and Hershey, G. K. (2002) Analysis of the life cycle of STAT6. Continuous cycling of STAT6 is required for IL-4 signaling. J. Biol. Chem. 277, 36563-36569
129. Schiemann, W. P., Bartoe, J. L. and Nathanson, N. M. (1997) Box 3-independent signaling mechanisms are involved in leukemia inhibitory factor receptor α- and gp130-mediated stimulation of mitogen-activated protein kinase. Evidence for participation of multiple signaling pathways which converge at Ras. J. Biol. Chem. 272, 16631-16636
130. Hermanns, H. M., Radtke, S., Schaper, F., Heinrich, P. C. and Behrmann, I. (2000) Non-redundant signal transduction of interleukin-6-type cytokines. The adapter protein She is specifically recruited to the oncostatin M receptor. J. Biol. Chem. 275, 40742-40748
131. Holgado-Madruga, M., Emlet, D. R., Moscatello, D. K., Godwin, A. K. and Wong, A. J. (1996) A Grb2-associated docking protein in EGF- and insulin-receptor signalling. Nature (London) 379, 560-564
132. Gu, H., Pratt, J. C., Burakoff, S. J. and Neel, B. G. (1998) Cloning of p97/Gab2, the major SHP2-binding protein in hematopoietic cells, reveals a novel pathway for cytokine-induced gene activation. Mol Cell 2, 729-740
133. 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 Jak1 and limits acute-phase protein expression. Biochem. J. 335, 557-565
134. Fukada, T., Hibi, M., Yamanaka, Y., Takahashi-Tezuka, M., Fujitani, Y., Yamaguchi, T., Nakajima, K. and Hirano, T. (1996) Two signals are necessary for cell proliferation induced by a cytokine receptor gp130: involvement of STAT3 in anti-apoptosis. Immunity 5, 449-460
135. Schaeper, U., Gehring, N. H., Fuchs, K. P., Sachs, M., Kempkes, B. and Birchmeier, W. (2000) Coupling of Gab1 to c-Met, Grb2, and Shp2 mediates biological responses. J. Cell Biol. 149, 1419-1432
136. Liu, Y. and Rohrschneider, L. R. (2002) The gift of Gab. FEBS Lett. 515, 1-7
137. Takahashi-Tezuka, M., Yoshida, Y., Fukada, T., Ohtani, T., Yamanaka, Y., Nishida, K., Nakajima, K., Hibi, M. and Hirano, T. (1998) Gab1 acts as an adapter molecule linking the cytokine receptor gp130 to ERK mitogen-activated protein kinase. Mol. Cell. Biol. 18, 4109-4117
138. Itch, M., Yoshida, Y., Nishida, K., Narimatsu, M., Hibi, M. and Hirano, T. (2000) Role of Gab1 in heart, placenta, and skin development and growth factor- and cytokine-induced extracellular signal-regulated kinase mitogen-activated protein kinase activation. Mol. Cell. Biol. 20, 3695-3704
139. Cunnick, J. M., Meng, S., Ren, Y., Desponts, C., Wang, H. G., Djeu, J. Y. and Wu, J. (2002) Regulation of the mitogen-activated protein kinase signaling pathway by SHP2. J. Biol. Chem. 277, 9498-9504
140. Zhang, S. Q., Tsiaras, W. G., Araki, T., Wen, G., Minichiello, L., Klein, R. and Neel, B. G. (2002) Receptor-specific regulation of phosphatidylinositol 3-kinase activation by the protein tyrosine phosphatase Shp2. Mol. Cell. Biol. 22, 4062-4072
141. Cacalano, N. A., Sanden, D. and Johnston, J. A. (2001) Tyrosine-phosphorylated SOCS-3 inhibits STAT activation but binds to p120 RasGAP and activates Ras. Nat. Cell Biol. 3, 460-465
142. Wang, Y., Robledo, O., Kinzie, E., Blanchard, F., Richards, C., Miyajima, A. and Baumann, H. (2000) Receptor subunit-specific action of oncostatin M in hepatic cells and its modulation by leukemia inhibitory factor. J. Biol. Chem. 275, 25273-25285
143. Bode, J. G., Ludwig, S., Freitas, C. A., Schaper, F., Ruhl, M., Melmed, S., Heinrich, P. C. and Häussinger, D. (2001) The MKK6/p38 mitogen-activated protein kinase pathway is capable of inducing SOCS3 gene expression and inhibits IL-6-induced transcription. Biol. Chem. 382, 1447-1453
144. Zauberman, A., Zipori, D., Krupsky, M. and Ben-Levy, R. (1999) Stress activated protein kinase p38 is involved in IL-6 induced transcriptional activation of STAT3. Oncogene 18, 3886-3893
145. Negoro, S., Oh, H., Tone, E., Kunisada, K., Fujio, Y., Walsh, K., Kishimoto, T. and Yamauchi-Takihara, K. (2001) Glycoprotein 130 regulates cardiac myocyte survival in doxorubicin-induced apoptosis through phosphatidylinositol 3-kinase/Akt phosphorylation and Bcl-xL/caspase-3 interaction. Circulation 103, 555-561
146. Jee, S. H., Chiu, H. C., Tsai, T. F., Tsai, W. L., Liao, Y. H., Chu, C. Y. and Kuo, M. L. (2062) The phosphatidyl inositol 3-kinase/Akt signal pathway is involved in interleukin-6-mediated Mcl-1 upregulation and anti-apoptosis activity in basal cell carcinoma cells. J. Invest. Dermatol. 119, 1121-1127
147. Shi, Y., Hsu, J. H., Hu, L., Gera, J. and Lichtenstein, A. (2802) Signal pathways involved in activation of p70S6K and phosphorylation of 4E-BP1 following exposure of multiple myeloma tumor cells to interleukin-6. J. Biol. Chem. 277, 15712-15720
148. Hsu, J. H., Shi, Y., Hu, L., Fisher, M., Franke, T. F. and Lichtenstein, A. (2002) Role of the AKT kinase in expansion of multiple myeloma clones: effects on cytokine-dependent proliferative and survival responses. Oncogene 21, 1391-1400
149. Hideshima, T., Nakamura, N., Chauhan, D. and Anderson, K. C. (2001) Biologic sequelae of interleukin-6 induced PI3-K/Akt signaling in multiple myeloma. Oncogene 20, 5991-6000
150. Chen, B. H., Chang, M. C., Su, Y. H., Tsai, Y. T. and Kuo, M. L. (1999) Interleukin-6 inhibits transforming growth factor-β-induced apoptosis through the phosphatidylinositol 3-kinase/Akt and signal transducers and activators of transcription 3 pathways. J. Biol. Chem. 274, 23013-23019
151. Kortylewski, M., Feld, F., Krüger, K. D., Bahrenberg, G., Roth, R. A., Joost, H. G., Heinrich, P. C., Behrmann, I. and Barthel, A. (2003) Akt modulates STAT3-mediated gene expression through a FKHR (FOXO1a)-dependent mechanism. J. Biol. Chem. 278, 5242-5249
152. Burfoot, M. S., Rogers, N. C., Watling, D., Smith J. M., Pons, S., Paonessaw, G., Pellegrini, S., White, M. F. and Kerr, I. M. (1997) Janus kinase-dependent activation of insulin receptor substrate 1 in response to interleukin-4, oncostatin M, and the interferons. J. Biol. Chem. 272, 24183-24190
153. Boulton, T. G., Stahl, N. and Yancopoulos, G. D. (1994) Ciliary neurotrophic factor/leukemia inhibitory factor/interleukin 6/oncostatin M family of cytokines induces tyrosine phosphorylation of a common set of proteins overlapping those induced by other cytokines and growth factors. J. Biol. Chem. 269, 11648-11655
154. Hof, P., Pluskey, S., Dhepaganon, S., Eck, M. J. and Shoelson, S. E. (1998) Crystal structure of the tyrosine phosphatase SHP-2. Cell (Cambridge, Mass.) 92, 441-450
155. Lechleider, R. J., Sugimoto, S., Bennett, A. M., Kashishian, A. S., Cooper, J. A., Shoelson, S. E., Walsh, C. T. and Neel, B. G. (1993) Activation of the SH2-containing phosphotyrosine phosphatase SH-PTP2 by its binding site, phosphotyrosine 1009, on the human plateled-derived growth factor receptor. J. Biol. Chem. 268, 21478-21481
156. Sugimoto, S., Wandless, T. J., Shoelson, S. E., Neel, B. G. and Walsh, C. T. (1994) Activation of the SH2-containing protein tyrosine phosphatase, SH-PTP2, by phosphotyrosine-containing peptides derived from insulin receptor substrate-1. J. Biol. Chem. 269, 13614-13622
157. Pluskey, S., Wandless, T. J., Walsh, C. T. and Shoelson, S. E. (1995) Potent stimulation of SH-PTP2 phosphatase activity by simultaneous occupancy of both SH2 domains. J. Biol. Chem. 270, 2897-2900
158. Lu, W., Gong, D., Bar-Sagi, D. and Cole, P. A. (2001) Site-specific incorporation of a phosphotyrosine mimetic reveals a role for tyrosine phosphorylation of SHP-2 in cell signaling. Mol. Cell 8, 759-769
159. Symes, A., Stahl, N., Reeves, S. A., Farruggella, T., Servidei, T., Gearan, T., Yancopoulos, G. and Fink, J. S. (1997) The protein tyrosine phosphatase SHP-2 negatively regulates ciliary neurotrophic factor induction of gene expression. Curr. Biol. 7, 697-700
160. Kim, H. K., Hawley, T. S., Hawley, R. G. and Baumann, H. (1998) Protein tyrosine phosphatase 2 (SHP-2) moderates signaling by gp130 but is not required for the induction of acute-phase plasma protein genes in hepatic cells. Mol. Cell. Biol. 18, 1525-1533
161. Anhuf, D., Weiussenbach, 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
162. Lehmann, U., Schmitz, J., Weissenbach, M., Sobota, R. M., Hörtner, M., Friederichs, K., Behrmann, I., Tsiaris, W., Sasaki, A., Schneider-Mergener, J. et al. (2003) SHP2 and SOCS3 contribute to Tyr-759-dependent attenuation of interleukin-6 signaling through gp130. J. Biol. Chem. 278, 661-671
163. Ohtani, T., Ishihara, K., Atsumi, T., Nishida, K., Kaneko, Y., Miyata, T., Itch, S., Narimatsu, M., Maeda, H., Fukada, T., et al. (2000) Dissection of signaling cascades through gp130 in vivo: reciprocal roles for STAT3- and SHP2-mediated signals in immune responses. Immunity 12, 95-105
164. Yin, T. G., Shen, R., Feng, G. S. and Yang, Y. C. (1997) Molecular characterization of specific interactions between SHP-2 phosphatase and JAK tyrosine kinases. J. Biol. Chem. 272, 1032-1037
165. Gunaje, J. J. and Bhat, G. J. (2001) Involvement of tyrosine phosphatase PTP1D in the inhibition of interleukin-6-induced Stat3 signaling by α-thrombin. Biochem. Biophys. Res. Commun. 288, 252-257
166. Wu, T. R., Hong, Y. K., Wang, X. D., Ling, M. Y., Dragoi, A. M., Chung, A. S., Campbell, A. G., Han, Z. Y., Feng, G. S. and Chin, Y. E. (2002) SHP-2 is a dual-specificity phosphatase involved in Stat1 dephosphorylation at both tyrosine and serine residues in nuclei. J. Biol. Chem. 277, 47572-47580
167. Shuai, K., Liao, J. and Song, M. M. (1996) Enhancement of antiproliferative activity of γ interferon by the specific inhibition of tyrosine dephosphorylation of Stat1. Mol. Cell. Biol. 16, 4932-4941
168. Sasse, J., Hemmann, U., Schwartz, C., Schniertshauer, U., Heesel, B., Landgraf, C., Schneider-Mergener, J., Heinrich, P. C. and Horn, F. (1997) Mutational analysis of acute-phase response factor Stat3 activation and dimerization. Mol. Cell. Biol. 17, 4677-4686
169. Strehlow, I. and Schindler, C. (1998) N-terminal signal transducer and activator of transcription (STAT) domains regulate nuclear translocation and STAT deactivation. J. Biol. Chem. 273, 28049-28056.
170. Tanuma, N., Nakamura, K., Shima, H. and Kikuchi, K. (2000) Protein-tyrosine phosphatase PTPε C inhibits Jak-STAT signaling and differentiation induced by interleukin-6 and leukemia inhibitory factor in M1 leukemia cells. J. Biol. Chem. 275, 28216-28221
171. Tanuma, N., Shima, H., Nakamura, K. and Kikuchi, K. (2001) Protein tyrosine phosphatase εC selectively inhibits interleukin-6- and interleukin-10-induced JAK-STAT signaling. Blood 98, 3030-3034
172. Myers, M. P., Andersen, J. N., Cheng, A., Tremblay, M. L., Horvath, C. M., Parisien, J. P., Salmeen, A., Barford, D. and Tonks, N. K. (2001) TYK2 and JAK2 are substrates of protein-tyrosine phosphatase 1B. J. Biol. Chem. 276, 47771-47774
173. Irie-Sasaki, J., Sasaki, T., Matsumoto, W., Opavsky, A., Cheng, M., Welstead, G., Griffiths, E., Krawczyk, C., Richardson, C. D., Aitken, K. et al. (2001) CD45 is a JAK phosphatase and negatively regulates cytokine receptor signalling. Nature (London) 409, 349-354
174. Bousquet, C., Susini, C. and Melmed, S. (1999) Inhibitory roles for SHP-1 and SOCS-3 following pituitary proopiomelanocortin induction by leukemia inhibitory factor. J. Clin. Invest. 104, 1277-1285
175. Haspel, R. L., Salditt-Georgieff, M. and Darnell, Jr, J. E. (1996) The rapid inactivation of nuclear tyrosine phosphorylated Stat1 depends upon a protein tyrosine phosphatase. EMBO J. 15, 6262-6268
176. ten Hoeve, J., de Jesus Ibarra-Sanchez, M., Fu, Y., Zhu, W., Tremblay, M., David, M. and Shuai, K. (2002) Identification of a nuclear Stall protein tyrosine phosphatase. Mol. Cell. Biol. 22, 5662-5668
177. Yamamoto, T., Sekine, Y., Kashima, K., Kubota, A., Sato, N., Aoki, N. and Matsuda, T. (2002) The nuclear isoform of protein-tyrosine phosphatase TC-PTP regulates interleukin-6-mediated signaling pathway through STAT3 dephosphorytation. Biochem. Biophys. Res. Commun. 297, 811-817
178. Zhu, W., Mustelin, T. and David, M. (2002) Arginine methylation of STAT1 regulates its dephosphorylation by T cell protein tyrosine phosphatase. J. Biol. Chem. 277, 35787-35790
179. Valdez, B. C., Henning, D., Perlaky, L., Busch, R. K. and Busch, H. (1997) Cloning and characterization of Gu/RH-II binding protein. Biochem. Biophys. Res. Commun. 234, 335-340
180. Chung, C. D., Liao, J., Liu, B., Rao, X., Jay, P., Berta, P. and Shuai, K. (1997) Specific inhibition of Stat3 signal transduction by PIAS3. Science (Washington, D.C.) 278, 1803-1805
181. Liu, B., Liao, J., Rao, X., Kushner, S. A., Chung, C. D., Chang, D. D. and Shuai, K. (1998) Inhibition of Stat1-mediated gene activation by PIAS1. Proc. Natl. Acad. Sci. U.S.A. 95, 10626-10631
182. Gross, M., Liu, B., Tan, J., French, F. S., Carey, M. and Shuai, K. (2001) Distinct effects of PIAS proteins on androgen-mediated gene activation in prostate cancer cells. Oncogene 20, 3880-3887
183. Liu, B., Gross, M., ten Hoeve, J. and Shuai, K. (2001) A transcriptional corepressor of Stat1 with an essential LXXLL signature motif. Proc. Natl. Acad. Sci. U.S.A. 98, 3203-3207
184. 2-terminal kinase activation. J. Biol. Chem. 276, 36624-36631
185. Rödel, B., Tavassoli, K., Karsunky, H., Schmidt, T., Bachmann, M., Schaper, F., Heinrich, P., Shuai, K., Elässer, H. P. and Möröy, T. (2000) The zinc finger protein Gfi-1 can enhance STAT3 signaling by interacting with the STAT3 inhibitor PIAS3. EMBO J. 19, 5845-5855
186. Tan, J. A., Hall, S. H., Hamil, K. G., Grossman, G., Petrusz, P. and French, F. S. (2002) Protein inhibitors of activated STAT resemble scaffold attachment factors and function as interacting nuclear receptor coregulators. J. Biol. Chem. 277, 16993-17001
187. Kotaia, N., Karvonen, U., Janne, O. A. and Palvimo, J. J. (2002) PIAS proteins modulate transcription factors by functioning as SUMO-1 ligases. Mol. Cell. Biol. 22, 5222-5234
188. Sachdev, S., Bruhn, L., Sieber, H., Pichler, A., Melchior, F. and Grosschedl, R. (2001) PIASy, a nuclear matrix-associated SUMO E3 ligase, represses LEF1 activity by sequestration into nuclear bodies. Genes Dev. 15, 3088-3103
189. Jackson, P. K. (2001) A new RING for SUMO: wrestling transcriptional responses into nuclear bodies with PIAS family E3 SUMO ligases. Genes Dev. 15, 3053-3058
190. Yoshimura, A., Ohkubo, T., Kiguchi, T., Jenkins, N. A., Gilbert, D. J., Copeland, N. G., Hara, T. and Miyajima, A. (1995) A novel cytokine-inducible gene CIS encodes an SH2-containing protein that binds to tyrosine-phosphorylated interleukin 3 and erythropoietin receptors. EMBO J. 14, 2816-2826
191. Matsumoto, A., Masuhara, M., Mitsui, K., Yokouchi, M., Ohtsubo, M., Misawa, H., Miyajima, A. and Yoshimura, A. (1997) CIS, a cytokine inducible SH2 protein, is a target of the JAK-STAT5 pathway and modulates STAT5 activation. Blood 89, 3148-3154
192. 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. Nature (London) 387, 917-921
193. Endo, T. A., Masuhara, M., Yokouchi, M., Suzuki, R., Sakamoto, H., Mitsui, K., Matsumoto, A., Tanimura, S., Ohtsubo, M., Misawa, H. et al. (1997) A new protein containing an SH2 domain that inhibits JAK kinases. Nature (London) 387, 921-924
194. Naka, T., Narazaki, M., Hirata, M., Matsumoto, T., Minamoto, S., Aono, A., Nishimoto, N., Kajita, T., Taga, T., Yoshizaki, K. et al. (1997) Structure and function of a new STAT-induced STAT inhibitor. Nature (London) 387, 924-929
195. Magrangeas, F., Boisteau, O., Denis, S., Jacques, Y. and Minvielle, S. (2001) Negative cross-talk between interleukin-3 and interleukin-11 is mediated by suppressor of cytokine signalling-3 (SOCS-3). Biochem. J. 353, 223-230
196. Verdier, F., Chretien, S., Muller, O., Varlet, P., Yoshimura, A., Gisselbrecht, S., Lacombe, C. and Mayeux, P. (1998) Proteasomes regulate erythropoietin receptor and signal transducer and activator of transcription 5 (STAT5) activation. Possible involvement of the ubiquitinated CIS protein. J. Biol. Chem. 273, 28185-28190
197. Yasukawa, H., Misawa, H., Sakamoto, H., Masuhara, M., Sasaki, A., Wakioka, T., Ohtsuka, S., Imaizumi, T., Matsuda, T., Ihle, J. N. and Yoshimura, A. (1999) The JAK-binding protein JAB inhibits Janus tyrosine kinase activity through binding in the activation loop. EMBO J. 18 1309-1320
198. Sasaki, A., Yasukawa, H., Suzuki, A., Kamizono, S., Syoda, T., Kinjyo, I., Sasaki, M., Johnston, J. A. and Yoshimura, A. (1999) Cytokine-inducible SH2 protein-3 (CIS3/SOCS3) inhibits Janus tyrosine kinase by binding through the N-terminal kinase inhibitory region as well as SH2 domain. Genes Cells 4, 339-351
199. 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, 12848-12856
200. Nicholson, S. E., De Souza, D., Fabri, L. J., Corbin, J., Willson, T. A., Zhang, J. G., Silva, A., Asimakis, M., Farley, A., Nash, A. D. et al. (2000) Suppressor of cytokine signaling-3 preferentially binds to the SHP-2-binding site on the shared cytokine receptor subunit gp130. Proc. Natl. Acad. Sci. U.S.A. 97, 6493-6498
201. Sasaki, A., Yasukawa, H., Shouda, T., Kitamura, T., Dikic, I. and Yoshimura, A. (2000) CIS3/SOCS-3 suppresses erythropoietin (EPO) signaling by binding the EPO receptor and JAK2. J. Biol. Chem. 275, 29338-29347
202. Eyckerman, S., Broekaert, D., Verhee, A., Vandekerckhove, J. and Tavernier, J. (2000) Identification of the Y985 and Y1077 motifs as SOCS3 recruitment sites in the murine leptin receptor. FEBS Lett. 486, 33-37
203. Bjørbæk, C., Lavery, H. J., Bates, S. H., Olson, R. K., Davis, S. M., Flier, J. S. and Myers, Jr, M. G. (2000) SOCS3 mediates feedback inhibition of the leptin receptor via Tyr 985. J. Biol. Chem. 275, 40649-40657
204. Hörtner, M., Nielsch, U., Mayr, L. M., Johnston, J. A., Heinrich, P. C. and Haan, S. (2002) Suppressor of cytokine signaling-3 is recruited to the activated granulocyte-colony stimulating factor receptor and modulates its signal transduction. J. Immunol. 169, 1219-1227
205. Hörtner, M., Nielsch, U., Mayr, L. M., Heinrich, P. C. and Haan, S. (2002) A new high affinity binding site for suppressor of cytokine signaling-3 on the erythropoietin receptor. Eur. J. Biochem. 269, 2516-2526
206. De Sauza, D., Fabri, L. J., Nash, A., Hilton, D. J., Nicola, N. A. and Baca, M. (2002) SH2 domains from suppressor of cytokine signaling-3 and protein tyrosine phosphatase SHP-2 have similar binding specificities. Biochemistry 41, 9229-9236
207. Nicholson, S. E., Willson, T. A., Farley, A., Starr, R., Zhang, J. G., Baca, M., Alexander, W. S., Metcalf, D., Hilton, D. J. and Nicola, N. A. (1999) Mutational analyses of the SOCS proteins suggest a dual domain requirement but distinct mechanisms for inhibition of LIF and IL-6 signal transduction. EMBO J. 18, 375-385
208. Zhang, J. G., Farley, A., Nicholson, S. E., Willson, T. A., Zugaro, L. M., Simpson, R. J., Moritz, R. L., Cary, D., Richardson, R., Hausmann, G. et al. (1999) The conserved SOCS box motif in suppressors of cytokine signaling binds to elongins B and C and may couple bound proteins to proteasomal degradation. Proc. Natl. Acad. Sci. U.S.A. 96, 2071-2076
209. Kamura, T., Sato, S., Haque, D., Liu, L., Kaelin, W. G. J., Conaway, R. C. and Conaway, J. W. (1998) The Elongin BC complex interacts with the conserved SOCS-box motif present in members of the SOCS, ras, WD-40 repeat, and ankyrin repeat families. Genes Dev. 12, 3872-3881
210. Frantsve, J., Schwaller, J., Sternberg, D. W., Kutok, J. and Gilliland, D. G. (2001) Socs-1 inhibits TEL-JAK2-mediated transformation of hematopoietic cells through inhibition of JAK2 kinase activity and induction of proteasome-mediated degradation. Mol. Cell. Biol. 21, 3547-3557
211. Kamizono, S., Hanada, T., Yasukawa, H., Minoguchi, S., Kato, R., Minoguchi, M., Hattori, K., Hatakeyama, S., Yada, M., Morita, S. et al. (2001) The SOCS box of SOCS-1 accelerates ubiquitin-dependent proteolysis of TEL-JAK2 J. Biol. Chem. 276, 12530-12538
212. Ungureanu, D., Saharinen, P., Junttila, I., Hilton, D. J. and Silvennoinen, O. (2002) Regulation of Jak2 through the ubiquitin-proteasome pathway involves phosphorylation of Jak2 on Y1007 and interaction with SOCS-1. Mol. Cell. Biol. 22, 3316-3326
213. Rui, L., Yuan, M., Frantz, D., Shoelson, S. and White, M. F. (2002) SOCS-1 and SOCS-3 block insulin signaling by ubiquitin-mediated degradation of IRS1 and IRS2. J. Biol. Chem. 277, 42394-42398
214. De Sepulveda, P., Ilangumaran, S. and Rottapel, R. (2000) Suppressor of cytokine signaling-1 inhibits VAV function through protein degradation. J. Biol. Chem. 275, 14005-14008
215. Kamura, T., Burian, D., Yan, Q., Schmidt, S. L., Lane, W. S., Querido, E., Branton, P. E., Shilatifard, A., Conaway, R. C. and Conaway, J. W. (2001) Muf1, a novel Elongin BC-interacting leucine-rich repeat protein that can assemble with Cul5 and Rbx1 to reconstitute a ubiquitin ligase. J. Biol. Chem. 276, 29748-29753
216. Chen, X. P., Losman, J. A., Cowan, S., Donahue, E., Fay, S., Vuong, B. Q., Nawijn, M. C., Capece, D., Cohan, V. L. and Rothman, P. (2002) Pim serine/threonine kinases regulate the stability of Socs-1 protein. Proc. Natl. Acad. Sci. U.S.A. 99, 2175-2180
217. Hanada, T., Yoshida, T., Kinjyo, I., Minoguchi, S., Yasukawa, H., Kato, S., Mimata, H., Nomura, Y., Seki, Y., Kubo, M. and Yoshimura, A. (2001) A mutant form of JAB/SOCS1 augments the cytokine-induced JAK/STAT pathway by accelerating degradation of wild-type JAB/CIS family proteins through the SOCS-box. J. Biol. Chem. 276, 40746-40754
218. Cohney, S. J., Sanden, D., Cacalano, N. A., Yoshimura, A., Mui, A., Migone, T. S. and Johnston, J. A. (1999) SOCS-3 is tyrosine phosphorylated in response to interleukin-2 and suppresses STAT5 phosphorylation and lymphocyte proliferation. Mol. Cell. Biol. 19, 4980-4988
219. Winzen, R., Kracht, M., Ritter, B., Wilhelm, A., Chen, C. Y., Shyu, A. B., Muller, M., Gaestel, M., Resch, K. and Holtmann, H. (1999) The p38 MAP kinase pathway signals for cytokine-induced mRNA stabilization via MAP kinase-activated protein kinase 2 and an AU-rich region-targeted mechanism. EMBO J. 18, 4969-4980
220. Neininger, A., Kontoyiannis, D., Kotlyarov, A., Winzen, R., Eckert, R., Volk, H. D., Holtmann, H., Kollias, G. and Gaestel, M. (2002) MK2 targets AU-rich elements and regulates biosynthesis of tumor necrosis factor and interleukin-6 independently at different post-transcriptional levels. J. Biol. Chem. 277, 3065-3068
221. Chen, C. Y., Del Gatto-Konczak, F., Wu, Z. and Karin, M. (1998) Stabilization of interleukin-2 mRNA by the c-Jun NH2-terminal kinase pathway. Science (Washington, D.C.) 280, 1945-1949
222. Ming, X. F., Stoecklin, G., Lu, M., Looser, R. and Moroni, C. (2001) Parallel and independent regulation of interleukin-3 mRNA turnover by phosphatidylinositol 3-kinase and p38 mitogen-activated protein kinase. Mol. Cell. Biol. 21, 5778-5789
223. Bank, U., Kupper, B., Reinhold, D., Hoffmann, T. and Ansorge, S. (1999) Evidence for a crucial role of neutrophil-derived serine proteases in the inactivation of interleukin-6 at sites of inflammation. FEBS Lett. 461, 235-240
224. Siewert, E., Müller-Esterl, W., Starr, R., Heinrich, P. C. and Schaper, F. (1999) Different protein turnover of interleukin-6-type cytokine signalling components. Eur. J. Biochem. 265, 251-257
225. Gerhartz, C., Dittrich, E., Stoyan, T., Rose-John, S., Yasukawa, K., Heinrich, P. C. and Graeve, L. (1994) Biosynthesis and half-life of the interleukin-6 receptor and its signal transducer gp130. Eur. J. Biochem. 223, 265-274
226. Schaefer, T. S., Sanders, L. K. and Nathans, D. (1995) Cooperative transcriptional activity of Jun and Star3 β, a short form of Stat3. Proc. Natl. Acad. Sci. U.S.A. 92, 9097-9101
227. Chakraborty, A., White, S. M., Schaefer, T. S., Ball, E. D., Dyer, K. F. and Tweardy, D. J. (1996) Granulocyte colony-stimulating factor activation of Stat3α and Stat3β in immature normal and leukemic human myeloid cells. Blood 88, 2442-2449
228. Caldenhoven, E., van Dijk, T. B., Solari, R., Armstrong, J., Raaijmakers, J. A., Lammers, J. W., Koenderman, L. and de Groat, R. P. (1996) STAT3β, a splice variant of transcription factor STAT3, is a dominant negative regulator of transcription. J. Biol. Chem. 271, 13221-13227
229. Schaefer, T. S., Sanders, L. K., Park, O. K. and Nathans, D. (1997) Functional differences between Stat3α and Stat3β. Mol. Cell. Biol. 17, 5307-5316
230. Yoo, J. Y., Huso, D. L., Nathans, D. and Desiderio, S. (2002) Specific ablation of Stat3β distorts the pattern of Stat3-responsive gene expression and impairs recovery from endotoxic shock. Cell (Cambridge, Mass.) 108, 331-344
231. Bode, J. G., Nimmesgern, A., Schmitz, J., Schaper, F., Schmitt, M., Frisch, W., Häussinger, D., Heinrich, P. C. and Graeve, L. (1999) LPS and TNFα induce SOCS3 mRNA and inhibit IL-6-induced activation of STAT3 in macrophages. FEBS Lett. 463, 365-370
232. Stoiber, D., Kovarik, P., Cohney, S., Johnston, J. A., Steinlein, P. and Decker, T. (1999) Lipopolysaccharide induces in macrophages the synthesis of the suppressor of cytokine signaling 3 and suppresses signal transduction in response to the activating factor IFN-γ. J. Immunol. 163, 2640-2647
233. Ahmed, S. T. and Ivashkiv, L. B. (2000) Inhibition of IL-6 and IL-10 signaling and Stat activation by inflammatory and stress pathways. J. Immunol. 165, 5227-5237
234. Niemand, C., Nimmesgern, A., Haan, S., Fischer, P., Schaper, F., Rossaint, R., Heinrich, P. C. and Müller-Newen, G. (2003) Different sensitivities of IL-10- and IL-6-induced STAT3 activation towards SOCS3 induction and other inhibitory mechanisms in primary human macrophages. J. Immunol. 170, 3263-3272
235. Stoiber, D., Stockinger, S., Steinlein, P., Kovarik, J. and Decker, T. (2001) Listeria monocytogenes modulates macrophage cytokine responses through STAT serine phosphorytation and the induction of suppressor of cytokine signaling 3. J. Immunol. 166, 466-472
236. Sengupta, T. K., Talbot, E. S., Scherle, P. A. and Ivashkiv, L. B. (1998) Rapid inhibition of interleukin-6 signaling and Stat3 activation mediated by mitogen-activated protein kinases. Proc. Natl. Acad. Sci. U.S.A. 95, 11107-11112
237. Andus, T., Geiger, T., Hirano, T., Kishimoto, T. and Heinrich, P. C. (1988) Action of recombinant human interleukin 6, interleukin 1 β and tumor necrosis factor α on the mRNA induction of acute-phase proteins. Eur. J. Immunol. 18, 739-746
238. 2-macroglobulin expression is due to activation of NF-κB. J. Immunol. 167, 1469-1481
239. Kordula, T. and Travis, J. (1996) The role of Stat and C/EBP transcription factors in the synergistic activation of rat serine protease inhibitor-3 gene by interleukin-6 and dexamethasone. Biochem. J. 313, 1019-1027
240. Brown, R. T., Ades, I. Z. and Nordan, R. P. (1995) An acute phase response factor/NF-κB site downstream of the junB gene that mediates responsiveness to interleukin-6 in a murine plasmacytoma. J. Biol. Chem. 270, 31129-31136
241. Horvai, A. E., Xu, L., Korzus, E., Brard, G., Kalafus, D., Mullen, T. M., Rose, D. W., Rosenfeld, M. G. and Glass, C. K. (1997) Nuclear integration of JAK/STAT and Ras/AP-1 signaling by CBP and p300 Proc. Natl. Acad. Sci. U.S.A. 94, 1074-1079
242. Symes, A., Gearan, T., Eby, J. and Fink, J. S. (1997) Integration of Jak-Stat and AP-1 signaling pathways at the vasoactive intestinal peptide cytokine response element regulates ciliary neurotrophic factor-dependent transcription. J. Biol. Chem. 272, 9648-9654
243. Zhang, X., Wrzeszczynska, M. H., Horvath, C. M. and Darnell, Jr, J. E. (1999) Interacting regions in Stat3 and c-Jun that participate in cooperative transcriptional activation. Mol. Cell. Biol. 19, 7138-7146
244. Zhang, Z., Jones, S. Hagood, J. S., Fuentes, N. L. and Fuller, G. M. (1997) STAT3 acts as a co-activator of glucocorticoid receptor signaling. J. Biol. Chem. 272, 30607-30610
245. 2-macroglobulin gene Nucleic Acids Res. 17, 1121-1138
246. Wegenka, U. M., Buschmann, J., Lütticken, C., Heinrich, P. C. and Horn, F. (1993) Acute-phase response factor, a nuclear factor binding to acute-phase response elements, is rapidly activated by interleukin-6 at the posttranslatianal level. Mol. Cell. Biol. 13, 276-288
247. 2-macraglobulin gene. J. Biol. Chem. 276, 33576-33581
248. Zhang, Z. and Fuller, G. M. (1997) The competitive binding of STAT3 and NF-κB on an overlapping DNA binding site. Biochem. Biophys. Res. Commun. 237, 90-94
249. Zhang, Z. and Fuller, G. M. (2000) Interleukin 1β inhibits interleukin 6-mediated rat γ fibrinogen gene expression. Blood 96, 3466-3472
250. Hiroi, M. and Ohmori, Y. (2003) The transcriptional coactivator CREB-binding protein cooperates with STAT1 and NF-κ B for synergistic transcriptional activation of the CXC ligand 9/manokine induced by interferon-γ gene. J. Biol. Chem. 278, 651-660
251. Korzus, E., Torchia, J., Rose, D. W., Xu, L., Kurokawa, R., McInerney, E. M., Mullen, T. M., Glass, C. K. and Rosenfeld, M. G. (1998) Transcription factor-specific requirements for coactivators and their acetyltransferase functions. Science (Washington, D.C.) 279, 703-707
252. Zhang, J. J. Vinkemeier, U., Gu, W., Chakravarti, D., Horvath, C. M. and Darnell, Jr, J. E. (1996) Two contact regions between Stat1 and CBP/p300 in interferon γ signaling. Proc. Natl. Acad. Sci. U.S.A. 93, 15092-15096
253. Paulson, M., Pisharody, S., Pan, L., Guadagno, S., Mui, A. L. and Levy, D. E. (1999) Stat protein transactivatian domains recruit p300/CBP through widely divergent sequences. J. Biol. Chem. 274, 25343-25349
254. Pfitzner, E., Jahne, R., Wissler, M., Stoecklin, E. and Groner, B. (1998) p300/CREB-binding protein enhances the prolactin-mediated transcriptional induction through direct interaction with the transactivation domain of Stat5, but does not participate in the Stat5- mediated suppression of the glucacorticoid response. Mol. Endocrinol. 12, 1582-1593
255. Zhu, M., John, S., Berg, M. and Leonard, W. J. (1999) Functional association of Nmi with Stat5 and Stat1 in IL-2- and IFNγ-mediated signaling. Cell (Cambridge, Mass.) 96, 121-130
256. Luo, G. and Yu-Lee, L. (2000) Stat5b inhibits NFκB-mediated signaling. Mol. Endocrinol. 14, 114-123
257. Nakajima, H., Brindle, P. K., Handa, M. and Ihle, J. N. (2001) Functional interaction of STAT5 and nuclear receptor co-repressor SMRT: implications in negative regulation of STAT5-dependent transcription. EMBO J. 20, 6836-6844
258. Campos, S. P. and Baumann, H. (1992) Insulin is a prominent modulator of the cytokine-stimulated expression of acute-phase plasma protein genes. Mol. Cell. Biol. 12, 1789-1797.
259. Wang, Y., Ripperger, J., Fey, G. H., Samols, D., Kordula, T., Wetzler, M., Van Etten, R. A. and Baumann, H. (1999) Modulation of hepatic acute phase gene expression by epidermal growth factor and Src protein tyrosine kinases in murine and human hepatic cells. Hepatalogy 30, 682-697
260. Nakayama, K., Kim, K. W. and Miyajima, A. (2002) A novel nuclear zinc finger protein EZI enhances nuclear retention and transactivation of STAT3. EMBO J. 21, 6174-6184