Characterization of a dominant-active STAT that promotes tumorigenesis in Drosophila

Developmental Biology

Volumn 344, Issue 2, 2010, Pages 621-636

  Ekas, Laura A ^a   Cardozo, Timothy J ^a   Flaherty, Maria Sol ^a   McMillan, Elizabeth A ^a   Gonsalves, Foster C ^a   Bach, Erika A ^a  

^a NEW YORK UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

Constitutively active; Drosophila; In vitro reporter; In vivo reporter; JAK; Signal transduction; STAT; Structure function; Unpaired

Indexed keywords

JANUS KINASE; STAT PROTEIN; STAT92E PROTEIN; UNCLASSIFIED DRUG;

AMINO TERMINAL SEQUENCE; ARTICLE; CARBOXY TERMINAL SEQUENCE; CARCINOGENESIS; CONTROLLED STUDY; DNA BINDING; DROSOPHILA; FEMALE; NONHUMAN; PHENOTYPE; POINT MUTATION; PRIORITY JOURNAL; PROTEIN ANALYSIS; PROTEIN DEPHOSPHORYLATION; PROTEIN DNA INTERACTION; PROTEIN DOMAIN; PROTEIN FUNCTION; PROTEIN PHOSPHORYLATION; SEQUENCE ALIGNMENT; TRANSCRIPTION INITIATION; TRANSGENE; WESTERN BLOTTING;

EID: 77955308856     PISSN: 00121606     EISSN: 1095564X     Source Type: Journal    
DOI: 10.1016/j.ydbio.2010.05.497     Document Type: Article

References (105)

1. Agaisse H., Petersen U.M., Boutros M., Mathey-Prevot B., Perrimon N. Signaling Role of Hemocytes in Drosophila JAK/STAT-Dependent Response to Septic Injury. Dev. Cell 2003, 5:441-450.
2. Arbouzova N.I., Zeidler M.P. JAK/STAT signalling in Drosophila: insights into conserved regulatory and cellular functions. Development 2006, 133:2605-2616.
3. Ayala-Camargo A., Ekas L.A., Flaherty M.S., Baeg G.H., Bach E.A. The JAK/STAT pathway regulates proximo-distal patterning in Drosophila. Dev. Dyn. 2007, 236:2721-2730.
4. Bach E.A., Tanner J.W., Marsters S., Ashkenazi A., Aguet M., Shaw A.S., Schreiber R.D. Ligand-induced assembly and activation of the gamma interferon receptor in intact cells. Mol. Cell. Biol. 1996, 16:3214-3221.
5. Bach E.A., Vincent S., Zeidler M.P., Perrimon N. A sensitized genetic screen to identify novel regulators and components of the Drosophila janus kinase/signal transducer and activator of transcription pathway. Genetics 2003, 165:1149-1166.
6. Bach E.A., Ekas L.A., Ayala-Camargo A., Flaherty M.S., Lee H., Perrimon N., Baeg G.H. GFP reporters detect the activation of the Drosophila JAK/STAT pathway in vivo. Gene Expr. Patterns 2007, 7:323-331.
7. Baeg G.H., Zhou R., Perrimon N. Genome-wide RNAi analysis of JAK/STAT signaling components in Drosophila. Genes Dev. 2005, 19:1861-1870.
8. Baxter E.J., Scott L.M., Campbell P.J., East C., Fourouclas N., Swanton S., Vassiliou G.S., Bench A.J., Boyd E.M., Curtin N., Scott M.A., Erber W.N., Green A.R. Acquired mutation of the tyrosine kinase JAK2 in human myeloproliferative disorders. Lancet 2005, 365:1054-1061.
9. Becker S., Groner B., Muller C.W. Three-dimensional structure of the Stat3beta homodimer bound to DNA. Nature 1998, 394:145-151.
10. Binari R., Perrimon N. Stripe-specific regulation of pair-rule genes by hopscotch, a putative Jak family tyrosine kinase in Drosophila. Genes Dev. 1994, 8:300-312.
11. Blaskovich M.A., Sun J., Cantor A., Turkson J., Jove R., Sebti S.M. Discovery of JSI-124 (cucurbitacin I), a selective Janus kinase/signal transducer and activator of transcription 3 signaling pathway inhibitor with potent antitumor activity against human and murine cancer cells in mice. Cancer Res. 2003, 63:1270-1279.
12. Brand A.H., Perrimon N. Targeted gene expression as a means of altering cell fates and generating dominant phenotypes. Development 1993, 118:401-415.
13. Braunstein J., Brutsaert S., Olson R., Schindler C. STATs dimerize in the absence of phosphorylation. J. Biol. Chem. 2003, 278:34133-34140.
14. Bromberg J.F., Wrzeszczynska M.H., Devgan G., Zhao Y., Pestell R.G., Albanese C., Darnell J.E. Stat3 as an oncogene. Cell 1999, 98:295-303.
15. Brown S., Hu N., Hombria J.C. Identification of the first invertebrate interleukin JAK/STAT receptor, the Drosophila gene domeless. Curr. Biol. 2001, 11:1700-1705.
16. Brown S., Hu N., Hombria J.C. Novel level of signalling control in the JAK/STAT pathway revealed by in situ visualisation of protein-protein interaction during Drosophila development. Development 2003, 130:3077-3084.
17. Callus B.A., Mathey-Prevot B. SOCS36E, a novel Drosophila SOCS protein, suppresses JAK/STAT and EGF-R signalling in the imaginal wing disc. Oncogene 2002, 21:4812-4821.
18. Cardozo T., Totrov M., Abagyan R. Homology modeling by the ICM method. Proteins 1995, 23:403-414.
19. Chang H.C., Zhang S., Oldham I., Naeger L., Hoey T., Kaplan M.H. STAT4 requires the N-terminal domain for efficient phosphorylation. J. Biol. Chem. 2003, 278:32471-32477.
20. Chao J.L., Tsai Y.C., Chiu S.J., Sun Y.H. Localized Notch signal acts through eyg and upd to promote global growth in Drosophila eye. Development 2004, 131:3839-3847.
21. Chen X., Vinkemeier U., Zhao Y., Jeruzalmi D., Darnell J.E., Kuriyan J. Crystal structure of a tyrosine phosphorylated STAT-1 dimer bound to DNA. Cell 1998, 93:827-839.
22. Chen H.W., Chen X., Oh S.W., Marinissen M.J., Gutkind J.S., Hou S.X. mom identifies a receptor for the Drosophila JAK/STAT signal transduction pathway and encodes a protein distantly related to the mammalian cytokine receptor family. Genes Dev. 2002, 16:388-398.
23. Chen X., Bhandari R., Vinkemeier U., Van Den Akker F., Darnell J.E., Kuriyan J. A reinterpretation of the dimerization interface of the N-terminal domains of STATs. Protein Sci. 2003, 12:361-365.
24. Chiarle R., Simmons W.J., Cai H., Dhall G., Zamo A., Raz R., Karras J.G., Levy D.E., Inghirami G. Stat3 is required for ALK-mediated lymphomagenesis and provides a possible therapeutic target. Nat. Med. 2005, 11:623-629.
25. Darnell J.E. Validating Stat3 in cancer therapy. Nat. Med. 2005, 11:595-596.
26. DasGupta R., Kaykas A., Moon R.T., Perrimon N. Functional genomic analysis of the Wnt-wingless signaling pathway. Science 2005, 308:826-833.
27. Decker T., Kovarik P., Meinke A. GAS elements: a few nucleotides with a major impact on cytokine-induced gene expression. J. Interferon Cytokine Res. 1997, 17:121-134.
28. Dominguez M., Casares F. Organ specification-growth control connection: new in-sights from the Drosophila eye-antennal disc. Dev. Dyn. 2005, 232:673-684.
29. Duff J.L., Quinlan K.L., Paxton L.L., Naik S.M., Caughman S.W. Pervanadate mimics IFNgamma-mediated induction of ICAM-1 expression via activation of STAT proteins. J. Invest. Dermatol. 1997, 108:295-301.
30. Ekas L.A., Baeg G.H., Flaherty M.S., Ayala-Camargo A., Bach E.A. JAK/STAT signaling promotes regional specification by negatively regulating wingless expression in Drosophila. Development 2006, 133:4721-4729.
31. Flaherty M.S., Zavadil J., Ekas L.A., Bach E.A. Genome-wide expression profiling in the Drosophila eye reveals unexpected repression of notch signaling by the JAK/STAT pathway. Dev. Dyn. 2009, 238:2235-2253.
32. Flaherty M.S., Salis P., Evans C.J., Ekas L.A., Marouf A., Zavadil J., Banerjee U., Bach E.A. chinmo is a functional effector of the JAK/STAT pathway that regulates eye development, tumor formation and stem cell self-renewal in Drosophila. Dev Cell. 2010, 18(4):556-568.
33. Gilbert M.M., Weaver B.K., Gergen J.P., Reich N.C. A novel functional activator of the Drosophila JAK/STAT pathway, unpaired2, is revealed by an in vivo reporter of pathway activation. Mech. Dev. 2005, 122:939-948.
34. Hanratty W.P., Dearolf C.R. The Drosophila Tumorous-lethal hematopoietic oncogene is a dominant mutation in the hopscotch locus. Mol. Gen. Genet. 1993, 238:33-37.
35. Harrison D.A., Binari R., Nahreini T.S., Gilman M., Perrimon N. Activation of a Drosophila Janus kinase (JAK) causes hematopoietic neoplasia and developmental defects. EMBO J. 1995, 14:2857-2865.
36. Harrison D.A., McCoon P.E., Binari R., Gilman M., Perrimon N. Drosophila unpaired encodes a secreted protein that activates the JAK signaling pathway. Genes Dev. 1998, 12:3252-3263.
37. Hauck B., Gehring W.J., Walldorf U. Functional analysis of an eye specific enhancer of the eyeless gene in Drosophila. Proc Natl Acad Sci U S A 1999, 96:564-569.
38. Henriksen M.A., Betz A., Fuccillo M.V., Darnell J.E. Negative regulation of STAT92E by an N-terminally truncated STAT protein derived from an alternative promoter site. Genes Dev. 2002, 16:2379-2389.
39. Herz H.M., Chen Z., Scherr H., Lackey M., Bolduc C., Bergmann A. vps25 mosaics display non-autonomous cell survival and overgrowth, and autonomous apoptosis. Development 2006, 133:1871-1880.
40. Hombria J.C., Brown S., Hader S., Zeidler M.P. Characterisation of Upd2, a Drosophila JAK/STAT pathway ligand. Dev. Biol. 2005, 288:420-433.
41. Horvath C.M. STAT proteins and transcriptional responses to extracellular signals. Trends Biochem. Sci. 2000, 25:496-502.
42. Hou X.S., Melnick M.B., Perrimon N. Marelle acts downstream of the Drosophila HOP/JAK kinase and encodes a protein similar to the mammalian STATs. Cell 1996, 84:411-419.
43. Issigonis M., Tulina N., de Cuevas M., Brawley C., Sandler L., Matunis E. JAK-STAT signal inhibition regulates competition in the Drosophila testis stem cell niche. Science 2009, 326:153-156.
44. Ito K., Awano W., Suzuki K., Hiromi Y., Yamamoto D. The Drosophila mushroom body is a quadruple structure of clonal units each of which contains a virtually identical set of neurones and glial cells. Development 1997, 124:761-771.
45. James C., Ugo V., Le Couedic J.P., Staerk J., Delhommeau F., Lacout C., Garcon L., Raslova H., Berger R., Bennaceur-Griscelli A., Villeval J.L., Constantinescu S.N., Casadevall N., Vainchenker W. A unique clonal JAK2 mutation leading to constitutive signalling causes polycythaemia vera. Nature 2005, 434:1144-1148.
46. Janody F., Lee J.D., Jahren N., Hazelett D.J., Benlali A., Miura G.I., Draskovic I., Treisman J.E. A mosaic genetic screen reveals distinct roles for trithorax and polycomb group genes in Drosophila eye development. Genetics 2004, 166:187-200.
47. Jones A.V., Chase A., Silver R.T., Oscier D., Zoi K., Wang Y.L., Cario H., Pahl H.L., Collins A., Reiter A., Grand F., Cross N.C. JAK2 haplotype is a major risk factor for the development of myeloproliferative neoplasms. Nat. Genet. 2009, 41:446-449.
48. Juni N., Awasaki T., Yoshida K., Hori S.H. The Om (1E) mutation in Drosophila ananassae causes compound eye overgrowth due to tom retrotransposon-driven overexpression of a novel gene. Genetics 1996, 143:1257-1270.
49. Karsten P., Hader S., Zeidler M.P. Cloning and expression of Drosophila SOCS36E and its potential regulation by the JAK/STAT pathway. Mech. Dev. 2002, 117:343-346.
50. Karsten P., Plischke I., Perrimon N., Zeidler M.P. Mutational analysis reveals separable DNA binding and trans-activation of Drosophila STAT92E. Cell. Signal. 2006, 18:819-829.
51. Kilpivaara O., Mukherjee S., Schram A.M., Wadleigh M., Mullally A., Ebert B.L., Bass A., Marubayashi S., Heguy A., Garcia-Manero G., Kantarjian H., Offit K., Stone R.M., Gilliland D.G., Klein R.J., Levine R.L. A germline JAK2 SNP is associated with predisposition to the development of JAK2(V617F)-positive myeloproliferative neoplasms. Nat. Genet. 2009, 41:455-459.
52. Klueg K.M., Alvarado D., Muskavitch M.A., Duffy J.B. Creation of a GAL4/UAS-coupled inducible gene expression system for use in Drosophila cultured cell lines. Genesis 2002, 34:119-122.
53. Kretzschmar A.K., Dinger M.C., Henze C., Brocke-Heidrich K., Horn F. Analysis of Stat3 (signal transducer and activator of transcription 3) dimerization by fluorescence resonance energy transfer in living cells. Biochem. J. 2004, 377:289-297.
54. Lacronique V., Boureux A., Valle V.D., Poirel H., Quang C.T., Mauchauffe M., Berthou C., Lessard M., Berger R., Ghysdael J., Bernard O.A. A TEL-JAK2 fusion protein with constitutive kinase activity in human leukemia. Science 1997, 278:1309-1312.
55. Lambertsson A. The minute genes in Drosophila and their molecular functions. Adv. Genet. 1998, 38:69-134.
56. Lee T., Luo L. Mosaic analysis with a repressible cell marker for studies of gene function in neuronal morphogenesis. Neuron 1999, 22:451-461.
57. Levine R.L., Wadleigh M., Cools J., Ebert B.L., Wernig G., Huntly B.J., Boggon T.J., Wlodarska I., Clark J.J., Moore S., Adelsperger J., Koo S., Lee J.C., Gabriel S., Mercher T., D'Andrea A., Frohling S., Dohner K., Marynen P., Vandenberghe P., Mesa R.A., Tefferi A., Griffin J.D., Eck M.J., Sellers W.R., Meyerson M., Golub T.R., Lee S.J., Gilliland D.G. Activating mutation in the tyrosine kinase JAK2 in polycythemia vera, essential thrombocythemia, and myeloid metaplasia with myelofibrosis. Cancer Cell 2005, 7:387-397.
58. Levy D.E., Darnell J.E. Stats: transcriptional control and biological impact. Nat. Rev. Mol. Cell Biol. 2002, 3:651-662.
59. Li L., Shaw P.E. Elevated activity of STAT3C due to higher DNA binding affinity of phosphotyrosine dimer rather than covalent dimer formation. J. Biol. Chem. 2006, 281:33172-33181.
60. Liddle F.J., Alvarez J.V., Poli V., Frank D.A. Tyrosine phosphorylation is required for functional activation of disulfide-containing constitutively active STAT mutants. Biochemistry 2006, 45:5599-5605.
61. Lindsley D.L., Zimm G.G. The Genome of Drosophila melanogaster 1992.
62. Luo H., Hanratty W.P., Dearolf C.R. An amino acid substitution in the Drosophila hopTum-l Jak kinase causes leukemia-like hematopoietic defects. EMBO J. 1995, 14:1412-1420.
63. Luscombe N.M., Laskowski R.A., Thornton J.M. Amino acid-base interactions: a three-dimensional analysis of protein-DNA interactions at an atomic level. Nucleic Acids Res. 2001, 29:2860-2874.
64. Mao X., Ren Z., Parker G.N., Sondermann H., Pastorello M.A., Wang W., McMurray J.S., Demeler B., Darnell J.E., Chen X. Structural bases of unphosphorylated STAT1 association and receptor binding. Mol. Cell 2005, 17:761-771.
65. Mertens C., Zhong M., Krishnaraj R., Zou W., Chen X., Darnell J.E. Dephosphorylation of phosphotyrosine on STAT1 dimers requires extensive spatial reorientation of the monomers facilitated by the N-terminal domain. Genes Dev. 2006, 20:3372-3381.
66. Moberg K.H., Schelble S., Burdick S.K., Hariharan I.K. Mutations in erupted, the Drosophila ortholog of mammalian tumor susceptibility gene 101, elicit non-cell-autonomous overgrowth. Dev. Cell 2005, 9:699-710.
67. Morata G., Ripoll P. Minutes: mutants of drosophila autonomously affecting cell division rate. Dev. Biol. 1975, 42:211-221.
68. Mukherjee T., Hombria J.C., Zeidler M.P. Opposing roles for Drosophila JAK/STAT signalling during cellular proliferation. Oncogene 2005, 24:2503-2511.
69. Murphy T.L., Geissal E.D., Farrar J.D., Murphy K.M. Role of the Stat4 N domain in receptor proximal tyrosine phosphorylation. Mol. Cell. Biol. 2000, 20:7121-7131.
70. Neculai D., Neculai A.M., Verrier S., Straub K., Klumpp K., Pfitzner E., Becker S. Structure of the unphosphorylated STAT5a dimer. J. Biol. Chem. 2005, 280:40782-40787.
71. Novak U., Ji H., Kanagasundaram V., Simpson R., Paradiso L. STAT3 forms stable homodimers in the presence of divalent cations prior to activation. Biochem. Biophys. Res. Commun. 1998, 247:558-563.
72. Nybakken K., Vokes S.A., Lin T.Y., McMahon A.P., Perrimon N. A genome-wide RNA interference screen in Drosophila melanogaster cells for new components of the Hh signaling pathway. Nat. Genet. 2005, 37:1323-1332.
73. Olcaydu D., Harutyunyan A., Jager R., Berg T., Gisslinger B., Pabinger I., Gisslinger H., Kralovics R. A common JAK2 haplotype confers susceptibility to myeloproliferative neoplasms. Nat. Genet. 2009, 41:450-454.
74. Ota N., Brett T.J., Murphy T.L., Fremont D.H., Murphy K.M. N-domain-dependent nonphosphorylated STAT4 dimers required for cytokine-driven activation. Nat. Immunol. 2004, 5:208-215.
75. Rawlings J.S., Rennebeck G., Harrison S.M., Xi R., Harrison D.A. Two Drosophila suppressors of cytokine signaling (SOCS) differentially regulate JAK and EGFR pathway activities. BMC Cell Biol. 2004, 5:38.
76. Reich N.C., Liu L. Tracking STAT nuclear traffic. Nat. Rev. Immunol. 2006, 6:602-612.
77. Reynolds-Kenneally J., Mlodzik M. Notch signaling controls proliferation through cell-autonomous and non-autonomous mechanisms in the Drosophila eye. Dev. Biol. 2005, 285:38-48.
78. Rorth P. A modular misexpression screen in Drosophila detecting tissue-specific phenotypes. Proc. Natl. Acad. Sci. U.S.A. 1996, 93:12418-12422.
79. Schroder M., Kroeger K.M., Volk H.D., Eidne K.A., Grutz G. Preassociation of nonactivated STAT3 molecules demonstrated in living cells using bioluminescence resonance energy transfer: a new model of STAT activation?. J. Leukoc. Biol. 2004, 75:792-797.
80. Sefton L., Timmer J.R., Zhang Y., Beranger F., Cline T.W. An extracellular activator of the Drosophila JAK/STAT pathway is a sex-determination signal element. Nature 2000, 405:970-973.
81. Shuai K., Liao J., Song M.M. Enhancement of antiproliferative activity of gamma interferon by the specific inhibition of tyrosine dephosphorylation of Stat1. Mol. Cell. Biol. 1996, 16:4932-4941.
82. Silver D.L., Montell D.J. Paracrine signaling through the JAK/STAT pathway activates invasive behavior of ovarian epithelial cells in Drosophila. Cell 2001, 107:831-841.
83. Song H., Wang R., Wang S., Lin J. A low-molecular-weight compound discovered through virtual database screening inhibits Stat3 function in breast cancer cells. Proc. Natl. Acad. Sci. U.S.A. 2005, 102:4700-4705.
84. Spradling A.C., Stern D., Beaton A., Rhem E.J., Laverty T., Mozden N., Misra S., Rubin G.M. The Berkeley Drosophila Genome Project gene disruption project: Single P-element insertions mutating 25% of vital Drosophila genes. Genetics 1999, 153:135-177.
85. Stancato L.F., David M., Carter-Su C., Larner A.C., Pratt W.B. Preassociation of STAT1 with STAT2 and STAT3 in separate signalling complexes prior to cytokine stimulation. J. Biol. Chem. 1996, 271:4134-4137.
86. Stowers R.S., Schwarz T.L. A genetic method for generating Drosophila eyes composed exclusively of mitotic clones of a single genotype. Genetics 1999, 152:1631-1639.
87. Sun J., Blaskovich M.A., Jove R., Livingston S.K., Coppola D., Sebti S.M. Cucurbitacin Q: a selective STAT3 activation inhibitor with potent antitumor activity. Oncogene 2005, 24:3236-3245.
88. Sweitzer S.M., Calvo S., Kraus M.H., Finbloom D.S., Larner A.C. Characterization of a Stat-like DNA binding activity in Drosophila melanogaster. J. Biol. Chem. 1995, 270:16510-16513.
89. Thompson B.J., Mathieu J., Sung H.H., Loeser E., Rorth P., Cohen S.M. Tumor suppressor properties of the ESCRT-II complex component Vps25 in Drosophila. Dev. Cell 2005, 9:711-720.
90. Tourkine N., Schindler C., Larose M., Houdebine L.M. Activation of STAT factors by prolactin, interferon-gamma, growth hormones, and a tyrosine phosphatase inhibitor in rabbit primary mammary epithelial cells. J. Biol. Chem. 1995, 270:20952-20961.
91. Tsai Y.C., Sun Y.H. Long-range effect of upd, a ligand for Jak/STAT pathway, on cell cycle in Drosophila eye development. Genesis 2004, 39:141-153.
92. Tsai Y.C., J.G., Y., P.H., C., Posakony J.W., Barolo S., Kim J., Henry Sun Y. Upd/Jak/STAT signaling represses wg transcription to allow initiation of morphogenetic furrow in Drosophila eye development. Dev. Biol. 2007, 306:760-771.
93. Vaccari T., Bilder D. The Drosophila tumor suppressor vps25 prevents nonautonomous overproliferation by regulating notch trafficking. Dev. Cell 2005, 9:687-698.
94. Vinkemeier U., Moarefi I., Darnell J.E., Kuriyan J. Structure of the amino-terminal protein interaction domain of STAT-4. Science 1998, 279:1048-1052.
95. Wang Y., Levy D.E. C. elegans STAT cooperates with DAF-7/TGF-beta signaling to repress dauer formation. Curr. Biol. 2006, 16:89-94.
96. Wang Y., Levy D.E. C. elegans STAT: evolution of a regulatory switch. FASEB J. 2006, 20:1641-1652.
97. Xu T., Rubin G.M. Analysis of genetic mosaics in developing and adult Drosophila tissues. Development 1993, 117:1223-1237.
98. Xu X., Sun Y.L., Hoey T. Cooperative DNA binding and sequence-selective recognition conferred by the STAT amino-terminal domain. Science 1996, 273:794-797.
99. Yan R., Small S., Desplan C., Dearolf C.R., Darnell J.E. Identification of a Stat gene that functions in Drosophila development. Cell 1996, 84:421-430.
100. Yang E., Henriksen M.A., Schaefer O., Zakharova N., Darnell J.E. Dissociation time from DNA determines transcriptional function in a STAT1 linker mutant. J. Biol. Chem. 2002, 277:13455-13462.
101. Zeidler M.P., Perrimon N., Strutt D.I. Polarity determination in the Drosophila eye: a novel role for unpaired and JAK/STAT signaling. Genes Dev. 1999, 13:1342-1353.
102. Zeidler M.P., Bach E.A., Perrimon N. The roles of the Drosophila JAK/STAT pathway. Oncogene 2000, 19:2598-2606.
103. Zeidler M.P., Tan C., Bellaiche Y., Cherry S., Hader S., Gayko U., Perrimon N. Temperature-sensitive control of protein activity by conditionally splicing inteins. Nat. Biotechnol. 2004, 22:871-876.
104. Zhang X., Wrzeszczynska M.H., Horvath C.M., Darnell J.E. Interacting regions in Stat3 and c-Jun that participate in cooperative transcriptional activation. Mol. Cell. Biol. 1999, 19:7138-7146.
105. Zhong M., Henriksen M.A., Takeuchi K., Schaefer O., Liu B., ten Hoeve J., Ren Z., Mao X., Chen X., Shuai K., Darnell J.E. Implications of an antiparallel dimeric structure of nonphosphorylated STAT1 for the activation-inactivation cycle. Proc. Natl. Acad. Sci. U.S.A. 2005, 102:3966-3971.