The JAK-STAT Pathway at Twenty

Immunity

Volumn 36, Issue 4, 2012, Pages 503-514

  Stark, George R ^a   Darnell, James E ^b  

^a LERNER RESEARCH INSTITUTE   (United States)

^b ROCKEFELLER UNIVERSITY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

INTERFERON; JANUS KINASE; STAT PROTEIN;

ACETYLATION; CELL NUCLEUS; CELL SURFACE; CHROMATIN; HUMAN; METHYLATION; MITOCHONDRIAL RESPIRATION; NONHUMAN; PRIORITY JOURNAL; PROTEIN PHOSPHORYLATION; PROTEIN PROCESSING; PROTEIN PROTEIN INTERACTION; REVIEW; SIGNAL TRANSDUCTION; SUMOYLATION; TRANSCRIPTION REGULATION;

ANIMALS; CHROMATIN; HUMANS; INTERFERON REGULATORY FACTORS; INTERFERON TYPE I; JANUS KINASES; MITOCHONDRIA; PROTEIN PROCESSING, POST-TRANSLATIONAL; SIGNAL TRANSDUCTION; STAT TRANSCRIPTION FACTORS; TRANSCRIPTION, GENETIC;

EID: 84859992161     PISSN: 10747613     EISSN: 10974180     Source Type: Journal    
DOI: 10.1016/j.immuni.2012.03.013     Document Type: Review

References (118)

1. Akira S., Nishio Y., Inoue M., Wang X.J., Wei S., Matsusaka T., Yoshida K., Sudo T., Naruto M., Kishimoto T. Molecular cloning of APRF, a novel IFN-stimulated gene factor 3 p91-related transcription factor involved in the gp130-mediated signaling pathway. Cell 1994, 77:63-71.
2. Argetsinger L.S., Campbell G.S., Yang X., Witthuhn B.A., Silvennoinen O., Ihle J.N., Carter-Su C. Identification of JAK2 as a growth hormone receptor-associated tyrosine kinase. Cell 1993, 74:237-244.
3. Berridge M.J. Inositol trisphosphate and diacylglycerol: two interacting second messengers. Annu. Rev. Biochem. 1987, 56:159-193.
4. Blomstrom D.C., Fahey D., Kutny R., Korant B.D., Knight E. Molecular characterization of the interferon-induced 15-kDa protein. Molecular cloning and nucleotide and amino acid sequence. J. Biol. Chem. 1986, 261:8811-8816.
5. Bourne H.D., DeFranco A.L. Signal transduction and intracellular messengers. Oncogenes and the Molecular Origins of Cancer 1990, 97-124. Cold Spring Harbor Laboraty Press, Cold Spring Harbor, NY. R.A. Weinberg (Ed.).
6. Brivanlou A.H., Darnell J.E. Signal transduction and the control of gene expression. Science 2002, 295:813-818.
7. Campbell G.S., Meyer D.J., Raz R., Levy D.E., Schwartz J., Carter-Su C. Activation of acute phase response factor (APRF)/Stat3 transcription factor by growth hormone. J. Biol. Chem. 1995, 270:3974-3979.
8. Cayley P.J., Kerr I.M. Synthesis, characterisation and biological significance of (2'-5')oligoadenylate derivatives of NAD+, ADP-ribose and adenosine(5')tetraphospho(5')adenosine. Eur. J. Biochem. 1982, 122:601-608.
9. Chen H., Sun H., You F., Sun W., Zhou X., Chen L., Yang J., Wang Y., Tang H., Guan Y., et al. Activation of STAT6 by STING is critical for antiviral innate immunity. Cell 2011, 147:436-446.
10. Cheon H., Stark G.R. Unphosphorylated STAT1 prolongs the expression of interferon-induced immune regulatory genes. Proc. Natl. Acad. Sci. USA 2009, 106:9373-9378.
11. Cheon H., Yang J., Stark G.R. The functions of signal transducers and activators of transcriptions 1 and 3 as cytokine-inducible proteins. J. Interferon Cytokine Res. 2011, 31:33-40.
12. Christova R., Jones T., Wu P.J., Bolzer A., Costa-Pereira A.P., Watling D., Kerr I.M., Sheer D. P-STAT1 mediates higher-order chromatin remodelling of the human MHC in response to IFNgamma. J. Cell Sci. 2007, 120:3262-3270.
13. Clayton D.F., Darnell J.E. Changes in liver-specific compared to common gene transcription during primary culture of mouse hepatocytes. Mol. Cell. Biol. 1983, 3:1552-1561.
14. Clayton D.F., Harrelson A.L., Darnell J.E. Dependence of liver-specific transcription on tissue organization. Mol. Cell. Biol. 1985, 5:2623-2632.
15. Cox R.F. Quantitation of elongating form A and B RNA polymerases in chick oviduct nuclei and effects of estradiol. Cell 1976, 7:455-465.
16. Dale T.C., Imam A.M., Kerr I.M., Stark G.R. Rapid activation by interferon alpha of a latent DNA-binding protein present in the cytoplasm of untreated cells. Proc. Natl. Acad. Sci. USA 1989, 86:1203-1207.
17. Darnell J.E., Kerr I.M., Stark G.R. Jak-STAT pathways and transcriptional activation in response to IFNs and other extracellular signaling proteins. Science 1994, 264:1415-1421.
18. Decker T., Lew D.J., Cheng Y.S., Levy D.E., Darnell J.E. Interactions of alpha- and gamma-interferon in the transcriptional regulation of the gene encoding a guanylate-binding protein. EMBO J. 1989, 8:2009-2014.
19. Decker T., Lew D.J., Mirkovitch J., Darnell J.E. Cytoplasmic activation of GAF, an IFN-gamma-regulated DNA-binding factor. EMBO J. 1991, 10:927-932.
20. Derman E., Krauter K., Walling L., Weinberger C., Ray M., Darnell J.E. Transcriptional control in the production of liver-specific mRNAs. Cell 1981, 23:731-739.
21. Droescher M., Begitt A., Marg A., Zacharias M., Vinkemeier U. Cytokine-induced paracrystals prolong the activity of signal transducers and activators of transcription (STAT) and provide a model for the regulation of protein solubility by small ubiquitin-like modifier (SUMO). J. Biol. Chem. 2011, 286:18731-18746.
22. Firmbach-Kraft I., Byers M., Shows T., Dalla-Favera R., Krolewski J.J. tyk2, prototype of a novel class of non-receptor tyrosine kinase genes. Oncogene 1990, 5:1329-1336.
23. Fried M., Crothers D.M. Equilibria and kinetics of lac repressor-operator interactions by polyacrylamide gel electrophoresis. Nucleic Acids Res. 1981, 9:6505-6525.
24. Friedman R.L., Stark G.R. alpha-Interferon-induced transcription of HLA and metallothionein genes containing homologous upstream sequences. Nature 1985, 314:637-639.
25. Friedman R.L., Manly S.P., McMahon M., Kerr I.M., Stark G.R. Transcriptional and posttranscriptional regulation of interferon-induced gene expression in human cells. Cell 1984, 38:745-755.
26. Fu X.Y., Kessler D.S., Veals S.A., Levy D.E., Darnell J.E. ISGF3, the transcriptional activator induced by interferon alpha, consists of multiple interacting polypeptide chains. Proc. Natl. Acad. Sci. USA 1990, 87:8555-8559.
27. Gao X., Wang H., Yang J.J., Liu X., Liu Z.R. Pyruvate kinase m2 regulates gene transcription by acting as a protein kinase. Mol. Cell 2012, 45:598-609.
28. Gill G. Growth factors and their receptors. Oncogenes and the Molecular Origins of Cancer 1990, 67-97. Cold Spring Harbor Laborator Press, Cold Spring Harbor, NY. R.A. Weinberg (Ed.).
29. Gilman A.G. G proteins: transducers of receptor-generated signals. Annu. Rev. Biochem. 1987, 56:615-649.
30. Gough D.J., Corlett A., Schlessinger K., Wegrzyn J., Larner A.C., Levy D.E. Mitochondrial STAT3 supports Ras-dependent oncogenic transformation. Science 2009, 324:1713-1716.
31. Gough D.J., Sehgal P., Levy D.E. Nongenomic functions of STAT3. Jak-Stat Signaling: From Basics to Disease 2011, The Springer-Verlag GmbH, Wien. T. Decker, M. Müller (Eds.).
32. Hou J., Schindler U., Henzel W.J., Ho T.C., Brasseur M., McKnight S.L. An interleukin-4-induced transcription factor: IL-4 Stat. Science 1994, 265:1701-1706.
33. Hunter T. Oncogene products in the cytoplasm: The protein kinases. Oncogenes and the Molecular Origins of Cancer 1990, 142-174. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY. R.A. Weinberg (Ed.).
34. Isaacs A., Lindenmann J. Virus interference. I. The interferon. Proc. R. Soc. Lond. B Biol. Sci. 1957, 147:258-267.
35. Isaacs A., Lindenmann J., Valentine R.C. Virus interference. II. Some properties of interferon. Proc. R. Soc. Lond. B Biol. Sci. 1957, 147:268-273.
36. Iwasaki H., Kovacic J.C., Olive M., Beers J.K., Yoshimoto T., Crook M.F., Tonelli L.H., Nabel E.G. Disruption of protein arginine N-methyltransferase 2 regulates leptin signaling and produces leanness in vivo through loss of STAT3 methylation. Circ. Res. 2010, 107:992-1001.
37. Jacobson N.G., Szabo S.J., Weber-Nordt R.M., Zhong Z., Schreiber R.D., Darnell J.E., Murphy K.M. Interleukin 12 signaling in T helper type 1 (Th1) cells involves tyrosine phosphorylation of signal transducer and activator of transcription (Stat)3 and Stat4. J. Exp. Med. 1995, 181:1755-1762.
38. Johnston J.A., Kawamura M., Kirken R.A., Chen Y.Q., Blake T.B., Shibuya K., Ortaldo J.R., McVicar D.W., O'Shea J.J. Phosphorylation and activation of the Jak-3 Janus kinase in response to interleukin-2. Nature 1994, 370:151-153.
39. Kelly J.M., Gilbert C.S., Stark G.R., Kerr I.M. Differential regulation of interferon-induced mRNAs and c-myc mRNA by alpha- and gamma-interferons. Eur. J. Biochem. 1985, 153:367-371.
40. Kempe T.D., Swyryd E.A., Bruist M., Stark G.R. Stable mutants of mammalian cells that overproduce the first three enzymes of pyrimidine nucleotide biosynthesis. Cell 1976, 9:541-550.
41. Kerr I.M., Brown R.E., Hovanessian A.G. Nature of inhibitor of cell-free protein synthesis formed in response to interferon and double-stranded RNA. Nature 1977, 268:540-542.
42. Knight E., Darnell J.E. Distribution of 5 s RNA in HeLa cells. J. Mol. Biol. 1967, 28:491-502.
43. Knight E., Korant B.D. Fibroblast interferon induces synthesis of four proteins in human fibroblast cells. Proc. Natl. Acad. Sci. USA 1979, 76:1824-1827.
44. Komyod W., Bauer U.M., Heinrich P.C., Haan S., Behrmann I. Are STATS arginine-methylated?. J. Biol. Chem. 2005, 280:21700-21705.
45. Larner A.C., Jonak G., Cheng Y.S., Korant B., Knight E., Darnell J.E. Transcriptional induction of two genes in human cells by beta interferon. Proc. Natl. Acad. Sci. USA 1984, 81:6733-6737.
46. Larner A.C., David M., Feldman G.M., Igarashi K., Hackett R.H., Webb D.S., Sweitzer S.M., Petricoin E.F., Finbloom D.S. Tyrosine phosphorylation of DNA binding proteins by multiple cytokines. Science 1993, 261:1730-1733.
47. Lee J.L., Wang M.J., Chen J.Y. Acetylation and activation of STAT3 mediated by nuclear translocation of CD44. J. Cell Biol. 2009, 185:949-957.
48. Lee J.E., Yang Y.M., Liang F.X., Gough D.J., Levy D.E., Sehgal P.B. Nongenomic STAT5-dependent effects on Golgi apparatus and endoplasmic reticulum structure and function. Am. J. Physiol. Cell Physiol. 2012, 302:C804-C820.
49. Levy D., Darnell J.E. Interferon-dependent transcriptional activation: signal transduction without second messenger involvement?. New Biol. 1990, 2:923-928.
50. Levy D.E., Darnell J.E. Stats: transcriptional control and biological impact. Nat. Rev. Mol. Cell Biol. 2002, 3:651-662.
51. Levy D., Larner A., Chaudhuri A., Babiss L.E., Darnell J.E. Interferon-stimulated transcription: isolation of an inducible gene and identification of its regulatory region. Proc. Natl. Acad. Sci. USA 1986, 83:8929-8933.
52. Levy D.E., Kessler D.S., Pine R., Reich N., Darnell J.E. Interferon-induced nuclear factors that bind a shared promoter element correlate with positive and negative transcriptional control. Genes Dev. 1988, 2:383-393.
53. Levy D.E., Kessler D.S., Pine R., Darnell J.E. Cytoplasmic activation of ISGF3, the positive regulator of interferon-alpha-stimulated transcription, reconstituted in vitro. Genes Dev. 1989, 3:1362-1371.
54. Levy D.E., Lew D.J., Decker T., Kessler D.S., Darnell J.E. Synergistic interaction between interferon-alpha and interferon-gamma through induced synthesis of one subunit of the transcription factor ISGF3. EMBO J. 1990, 9:1105-1111.
55. Lew D.J., Decker T., Darnell J.E. Alpha interferon and gamma interferon stimulate transcription of a single gene through different signal transduction pathways. Mol. Cell. Biol. 1989, 9:5404-5411.
56. Liu X., Robinson G.W., Gouilleux F., Groner B., Hennighausen L. Cloning and expression of Stat5 and an additional homologue (Stat5b) involved in prolactin signal transduction in mouse mammary tissue. Proc. Natl. Acad. Sci. USA 1995, 92:8831-8835.
57. Lockart R.Z., Groman N.B. [Some factors influencing the interaction of Western equine encephalomyelitis and selected host cells]. J. Infect. Dis. 1958, 103:163-171.
58. Mandal M., Powers S.E., Maienschein-Cline M., Bartom E.T., Hamel K.M., Kee B.L., Dinner A.R., Clark M.R. Epigenetic repression of the Igk locus by STAT5-mediated recruitment of the histone methyltransferase Ezh2. Nat. Immunol. 2011, 12:1212-1220.
59. McKnight G.S., Palmiter R.D. Transcriptional regulation of the ovalbumin and conalbumin genes by steroid hormones in chick oviduct. J. Biol. Chem. 1979, 254:9050-9058.
60. Meissner T., Krause E., Lödige I., Vinkemeier U. Arginine methylation of STAT1: a reassessment. Cell 2004, 119:587-589. discussion 589-590.
61. Morrow A.N., Schmeisser H., Tsuno T., Zoon K.C. A novel role for IFN-stimulated gene factor 3II in IFN-γ signaling and induction of antiviral activity in human cells. J. Immunol. 2011, 186:1685-1693.
62. Mowen K.A., Tang J., Zhu W., Schurter B.T., Shuai K., Herschman H.R., David M. Arginine methylation of STAT1 modulates IFNalpha/beta-induced transcription. Cell 2001, 104:731-741.
63. Mui A.L., Wakao H., O'Farrell A.M., Harada N., Miyajima A. Interleukin-3, granulocyte-macrophage colony stimulating factor and interleukin-5 transduce signals through two STAT5 homologs. EMBO J. 1995, 14:1166-1175.
64. Müller M., Briscoe J., Laxton C., Guschin D., Ziemiecki A., Silvennoinen O., Harpur A.G., Barbieri G., Witthuhn B.A., Schindler C., et al. The protein tyrosine kinase JAK1 complements defects in interferon-alpha/beta and -gamma signal transduction. Nature 1993, 366:129-135.
65. Nagano Y., Kokima Y. Pouvoir immunisant du virus vaccinal inactive par des rayons ultraviolets. C.R. Soc. Bil. 1954, 48:1700-1702.
66. Ng S.L., Friedman B.A., Schmid S., Gertz J., Myers R.M., Tenoever B.R., Maniatis T. IκB kinase epsilon (IKK(epsilon)) regulates the balance between type I and type II interferon responses. Proc. Natl. Acad. Sci. USA 2011, 108:21170-21175.
67. Nie Y., Erion D.M., Yuan Z., Dietrich M., Shulman G.I., Horvath T.L., Gao Q. STAT3 inhibition of gluconeogenesis is downregulated by SirT1. Nat. Cell Biol. 2009, 11:492-500.
68. O'Shea J.J., Kanno Y., Chen X., Levy D.E. Cell signaling. Stat acetylation-a key facet of cytokine signaling?. Science 2005, 307:217-218.
69. 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. Mol. Cell. Biol. 1989, 9:4605-4612.
70. Pene J.J., Knight E., Darnell J.E. Characterization of a new low molecular weight RNA in HeLa cell ribosomes. J. Mol. Biol. 1968, 33:609-623.
71. Perwitasari O., Cho H., Diamond M.S., Gale M. Inhibitor of κB kinase epsilon (IKK(epsilon)), STAT1, and IFIT2 proteins define novel innate immune effector pathway against West Nile virus infection. J. Biol. Chem. 2011, 286:44412-44423.
72. Porter A.C., Chernajovsky Y., Dale T.C., Gilbert C.S., Stark G.R., Kerr I.M. Interferon response element of the human gene 6-16. EMBO J. 1988, 7:85-92.
73. Powell D.J., Friedman J.M., Oulette A.J., Krauter K.S., Darnell J.E. Transcriptional and post-transcriptional control of specific messenger RNAs in adult and embryonic liver. J. Mol. Biol. 1984, 179:21-35.
74. Rane S.G., Reddy E.P. JAK3: a novel JAK kinase associated with terminal differentiation of hematopoietic cells. Oncogene 1994, 9:2415-2423.
75. Reich N., Evans B., Levy D., Fahey D., Knight E., Darnell J.E. Interferon-induced transcription of a gene encoding a 15-kDa protein depends on an upstream enhancer element. Proc. Natl. Acad. Sci. USA 1987, 84:6394-6398.
76. Reid T.R., Hersh C.L., Kerr I.M., Stark G.R. Analysis of 2',5'-oligoadenylates in cells and tissues. Anal. Biochem. 1984, 136:136-141.
77. Ruff-Jamison S., Chen K., Cohen S. Induction by EGF and interferon-gamma of tyrosine phosphorylated DNA binding proteins in mouse liver nuclei. Science 1993, 261:1733-1736.
78. Sadowski H.B., Shuai K., Darnell J.E., Gilman M.Z. A common nuclear signal transduction pathway activated by growth factor and cytokine receptors. Science 1993, 261:1739-1744.
79. Schindler C., Fu X.Y., Improta T., Aebersold R., Darnell J.E. Proteins of transcription factor ISGF-3: one gene encodes the 91-and 84-kDa ISGF-3 proteins that are activated by interferon alpha. Proc. Natl. Acad. Sci. USA 1992, 89:7836-7839.
80. Schindler C., Shuai K., Prezioso V.R., Darnell J.E. Interferon-dependent tyrosine phosphorylation of a latent cytoplasmic transcription factor. Science 1992, 257:809-813.
81. Sehgal P.B., Levy D.E., Hirano T. Signal Transducers and Activators of Transcription (STATs): Activation and Biology 2003, Kluwer, Dordrecht, The Netherlands.
82. Sestito R., Madonna S., Scarponi C., Cianfarani F., Failla C.M., Cavani A., Girolomoni G., Albanesi C. STAT3-dependent effects of IL-22 in human keratinocytes are counterregulated by sirtuin 1 through a direct inhibition of STAT3 acetylation. FASEB J. 2011, 25:916-927.
83. Shen Y., Schlessinger K., Zhu X., Meffre E., Quimby F., Levy D.E., Darnell J.E. Essential role of STAT3 in postnatal survival and growth revealed by mice lacking STAT3 serine 727 phosphorylation. Mol. Cell. Biol. 2004, 24:407-419.
84. Shuai K. Regulation of cytokine signaling pathways by PIAS proteins. Cell Res. 2006, 16:196-202.
85. Shuai K., Schindler C., Prezioso V.R., Darnell J.E. Activation of transcription by IFN-gamma: tyrosine phosphorylation of a 91-kD DNA binding protein. Science 1992, 258:1808-1812.
86. Shuai K., Stark G.R., Kerr I.M., Darnell J.E. A single phosphotyrosine residue of Stat91 required for gene activation by interferon-gamma. Science 1993, 261:1744-1746.
87. Silvennoinen O., Schindler C., Schlessinger J., Levy D.E. Ras-independent growth factor signaling by transcription factor tyrosine phosphorylation. Science 1993, 261:1736-1739.
88. Stark G.R. My life in science, not the restaurant business. J. Biol. Chem. 2005, 280:9753-9760.
89. Stark G.R., Kerr I.M., Williams B.R., Silverman R.H., Schreiber R.D. How cells respond to interferons. Annu. Rev. Biochem. 1998, 67:227-264.
90. Stark G.R., Wang Y., Lu T. Lysine methylation of promoter-bound transcription factors and relevance to cancer. Cell Res. 2011, 21:375-380.
91. Szczepanek K., Chen Q., Derecka M., Salloum F.N., Zhang Q., Szelag M., Cichy J., Kukreja R.C., Dulak J., Lesnefsky E.J., Larner A.C. Mitochondrial-targeted Signal transducer and activator of transcription 3 (STAT3) protects against ischemia-induced changes in the electron transport chain and the generation of reactive oxygen species. J. Biol. Chem. 2011, 286:29610-29620.
92. Tahk S., Liu B., Chernishof V., Wong K.A., Wu H., Shuai K. Control of specificity and magnitude of NF-kappa B and STAT1-mediated gene activation through PIASy and PIAS1 cooperation. Proc. Natl. Acad. Sci. USA 2007, 104:11643-11648.
93. Takahashi T., Shirasawa T. Molecular cloning of rat JAK3, a novel member of the JAK family of protein tyrosine kinases. FEBS Lett. 1994, 342:124-128.
94. Tenoever B.R., Ng S.L., Chua M.A., McWhirter S.M., García-Sastre A., Maniatis T. Multiple functions of the IKK-related kinase IKKepsilon in interferon-mediated antiviral immunity. Science 2007, 315:1274-1278.
95. Testoni B., Völlenkle C., Guerrieri F., Gerbal-Chaloin S., Blandino G., Levrero M. Chromatin dynamics of gene activation and repression in response to interferon alpha (IFN(alpha)) reveal new roles for phosphorylated and unphosphorylated forms of the transcription factor STAT2. J. Biol. Chem. 2011, 286:20217-20227.
96. Ungureanu D., Vanhatupa S., Grönholm J., Palvimo J.J., Silvennoinen O. SUMO-1 conjugation selectively modulates STAT1-mediated gene responses. Blood 2005, 106:224-226.
97. Varinou L., Ramsauer K., Karaghiosoff M., Kolbe T., Pfeffer K., Müller M., Decker T. Phosphorylation of the Stat1 transactivation domain is required for full-fledged IFN-gamma-dependent innate immunity. Immunity 2003, 19:793-802.
98. Veals S.A., Schindler C., Leonard D., Fu X.Y., Aebersold R., Darnell J.E., Levy D.E. Subunit of an alpha-interferon-responsive transcription factor is related to interferon regulatory factor and Myb families of DNA-binding proteins. Mol. Cell. Biol. 1992, 12:3315-3324.
99. Velazquez L., Fellous M., Stark G.R., Pellegrini S. A protein tyrosine kinase in the interferon alpha/beta signaling pathway. Cell 1992, 70:313-322.
100. Wahl G.M., Padgett R.A., Stark G.R. Gene amplification causes overproduction of the first three enzymes of UMP synthesis in N-(phosphonacetyl)-L-aspartate-resistant hamster cells. J. Biol. Chem. 1979, 254:8679-8689.
101. Wakao H., Gouilleux F., Groner B. Mammary gland factor (MGF) is a novel member of the cytokine regulated transcription factor gene family and confers the prolactin response. EMBO J. 1994, 13:2182-2191.
102. Watling D., Guschin D., Müller M., Silvennoinen O., Witthuhn B.A., Quelle F.W., Rogers N.C., Schindler C., Stark G.R., Ihle J.N., Kerr I.M. Complementation by the protein tyrosine kinase JAK2 of a mutant cell line defective in the interferon-gamma signal transduction pathway. Nature 1993, 366:166-170.
103. 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. Mol. Cell. Biol. 1994, 14:3186-3196.
104. Wegrzyn J., Potla R., Chwae Y.J., Sepuri N.B., Zhang Q., Koeck T., Derecka M., Szczepanek K., Szelag M., Gornicka A., et al. Function of mitochondrial Stat3 in cellular respiration. Science 2009, 323:793-797.
105. Weichselbaum R.R., Ishwaran H., Yoon T., Nuyten D.S., Baker S.W., Khodarev N., Su A.W., Shaikh A.Y., Roach P., Kreike B., et al. An interferon-related gene signature for DNA damage resistance is a predictive marker for chemotherapy and radiation for breast cancer. Proc. Natl. Acad. Sci. USA 2008, 105:18490-18495.
106. Wen Z., Zhong Z., Darnell J.E. Maximal activation of transcription by Stat1 and Stat3 requires both tyrosine and serine phosphorylation. Cell 1995, 82:241-250.
107. Wilks A.F. Two putative protein-tyrosine kinases identified by application of the polymerase chain reaction. Proc. Natl. Acad. Sci. USA 1989, 86:1603-1607.
108. Wilks A.F., Harpur A.G., Kurban R.R., Ralph S.J., Zürcher G., Ziemiecki A. Two novel protein-tyrosine kinases, each with a second phosphotransferase-related catalytic domain, define a new class of protein kinase. Mol. Cell. Biol. 1991, 11:2057-2065.
109. Witthuhn B.A., Silvennoinen O., Miura O., Lai K.S., Cwik C., Liu E.T., Ihle J.N. Involvement of the Jak-3 Janus kinase in signalling by interleukins 2 and 4 in lymphoid and myeloid cells. Nature 1994, 370:153-157.
110. Yamamoto K., Quelle F.W., Thierfelder W.E., Kreider B.L., Gilbert D.J., Jenkins N.A., Copeland N.G., Silvennoinen O., Ihle J.N. Stat4, a novel gamma interferon activation site-binding protein expressed in early myeloid differentiation. Mol. Cell. Biol. 1994, 14:4342-4349.
111. Yan S.J., Lim S.J., Shi S., Dutta P., Li W.X. Unphosphorylated STAT and heterochromatin protect genome stability. FASEB J. 2011, 25:232-241.
112. Yang J., Chatterjee-Kishore M., Staugaitis S.M., Nguyen H., Schlessinger K., Levy D.E., Stark G.R. Novel roles of unphosphorylated STAT3 in oncogenesis and transcriptional regulation. Cancer Res. 2005, 65:939-947.
113. Yang J., Liao X., Agarwal M.K., Barnes L., Auron P.E., Stark G.R. Unphosphorylated STAT3 accumulates in response to IL-6 and activates transcription by binding to NFkappaB. Genes Dev. 2007, 21:1396-1408.
114. Yang J., Huang J., Dasgupta M., Sears N., Miyagi M., Wang B., Chance M.R., Chen X., Du Y., Wang Y., et al. Reversible methylation of promoter-bound STAT3 by histone-modifying enzymes. Proc. Natl. Acad. Sci. USA 2010, 107:21499-21504.
115. Yuan Z.L., Guan Y.J., Chatterjee D., Chin Y.E. Stat3 dimerization regulated by reversible acetylation of a single lysine residue. Science 2005, 307:269-273.
116. Yue H., Li W., Desnoyer R., Karnik S.S. Role of nuclear unphosphorylated STAT3 in angiotensin II type 1 receptor-induced cardiac hypertrophy. Cardiovasc. Res. 2010, 85:90-99.
117. Zhong Z., Wen Z., Darnell J.E. Stat3: a STAT family member activated by tyrosine phosphorylation in response to epidermal growth factor and interleukin-6. Science 1994, 264:95-98.
118. Zhong Z., Wen Z., Darnell J.E. Stat3 and Stat4: members of the family of signal transducers and activators of transcription. Proc. Natl. Acad. Sci. USA 1994, 91:4806-4810.