Tracking STAT nuclear traffic

Nature Reviews Immunology

Volumn 6, Issue 8, 2006, Pages 602-612

  Reich, Nancy C ^a   Liu, Ling ^a  

^a STONY BROOK UNIVERSITY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

INTERFERON REGULATORY FACTOR 9; PROTEIN; STAT PROTEIN; STAT1 PROTEIN; STAT2 PROTEIN; STAT5 PROTEIN; UNCLASSIFIED DRUG;

CELL NUCLEUS; CELLULAR DISTRIBUTION; CYTOPLASM; DNA BINDING; NONHUMAN; PRIORITY JOURNAL; PROTEIN PHOSPHORYLATION; REVIEW;

ACTIVE TRANSPORT, CELL NUCLEUS; ANIMALS; CELL NUCLEUS; DNA; HUMANS; INTERFERON-STIMULATED GENE FACTOR 3, GAMMA SUBUNIT; STAT TRANSCRIPTION FACTORS; STAT3 TRANSCRIPTION FACTOR; STAT5 TRANSCRIPTION FACTOR;

EID: 33746570647     PISSN: 14741733     EISSN: None     Source Type: Journal    
DOI: 10.1038/nri1885     Document Type: Review

References (124)

1. Darnell, J. E., Jr. STATs and gene regulation. Science 277, 1630-1635 (1997).
2. Ihle, J. N. The Stat family in cytokine signaling. Curr. Opin. Cell Biol. 13, 211-217 (2001).
3. Kisseleva, T., Bhattacharya, S., Braunstein, J. & Schindler, C. W. Signaling through the JAK/STAT pathway, recent advances and future challenges. Gene 285, 1-24 (2002).
4. Levy, D. E. & Darnell, J. E. J. Stats: transcriptional control and biological impact. Nature Rev. Mol. Cell Biol. 3, 651-662 (2002). An excellent review of basic mechanisms of STAT activation and function.
5. Stark, G. R., Kerr, I. M., Williams, B. R., Silverman, R. H. & Schreiber, R. D. How cells respond to interferons. Annu. Rev. Biochem. 67, 227-264 (1998).
6. Becker, S., Groner, B. & Muller, C. W. Three-dimensional structure of the Stat3β homodimer bound to DNA. Nature 394, 145-151 (1998).
7. Chen, X. et al. Crystal structure of a tyrosine phosphorylated STAT-1 dimer bound to DNA. Cell 93, 827-839 (1998).
8. Mao, X. et al. Structural bases of unphosphorylated STAT1 association and receptor binding. Mol. Cell 17, 761-771 (2005).
9. Neculai, D. et al. Structure of the unphosphorylated STAT5a dimer. J. Biol. Chem. 280, 40782-40787 (2005). References 6-9 solved the crystal structures of tyrosine phosphorylated STAT dimers bound to DNA, and unphosphorylated STAT oligomers.
10. 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. 271, 4134-4137 (1996).
11. Yamaoka, K. et al. The Janus kinases (Jaks). Genome Biol. 5, 253 (2004).
12. Yeh, T. C. & Pellegrini, S. The Janus kinase family of protein tyrosine kinases and their role in signaling. Cell. Mol. Life Sci. 55, 1523-1534 (1999).
13. Greenlund, A. C. et al. Stat recruitment by tyrosine-phosphorylated cytokine receptors: an ordered reversible affinity-driven process. Immunity 2, 677-687 (1995).
14. Marrero, M. B. et al. Direct stimulation of Jak/STAT pathway by the angiotensin II AT1 receptor. Nature 375, 247-250 (1995).
15. McWhinney, C. D., Dostal, D. & Baker, K. Angiotensin II activates Stat5 through Jak2 kinase in cardiac myocytes. J. Mol. Cell. Cardiol. 30, 751-761 (1998).
16. Mellado, M., Rodriguez-Frade, J. M., Manes, S. & Martinez, A. C. Chemokine signaling and functional responses: the role of receptor dimerization and TK pathway activation. Annu. Rev. Immunol. 19, 397-421 (2001).
17. Wong, M. & Fish, E. N. RANTES and MIP-Iα activate stats in T cells. J. Biol. Chem. 273, 309-314 (1998).
18. David, M. et al. STAT activation by epidermal growth factor (EGF) and amphiregulin. Requirement for the EGF receptor kinase but not for tyrosine phosphorylation sites or JAK1. J. Biol. Chem. 271, 9185-9188 (1996).
19. Olayioye, M. A., Beuvink, I., Horsch, K., Daly, J. M. & Hynes, N. E. ErbB receptor-induced activation of stat transcription factors is mediated by Src tyrosine kinases. J. Biol. Chem. 274, 17209-17218 (1999).
20. Park, O. K., Schaefer, T. S. & Nathans, D. In vitro activation of Stat3 by epidermal growth factor receptor kinase. Proc. Natl Acad. Sci. USA 93, 13704-13708 (1996).
21. Vignais, M. L., Sadowski, H. B., Watling, D., Rogers, N. C. & Gilman, M. Platelet-derived growth factor induces phosphorylation of multiple JAK family kinases and STAT proteins. Mol. Cell. Biol. 16, 1759-1769 (1996).
22. Yu, C. L. et al. Enhanced DNA-binding activity of a Stat3-related protein in cells transformed by the Src oncoprotein. Science 269, 81-83 (1995).
23. Benekli, M., Baer, M. R., Baumann, H. & Wetzler, M. Signal transducer and activator of transcription proteins in leukemias. Blood 101, 2940-2954 (2003).
24. Bowman, T., Garcia, R., Turkson, J. & Jove, R. STATs in oncogenesis. Oncogene 19, 2474-2488 (2000).
25. Danial, N. N. & Rothman, P. JAK-STAT signaling activated by Abl oncogenes. Oncogene 19, 2523-2531 (2000).
26. Akira, S. Functional roles of STAT family proteins: lessons from knockout mice. Stem Cells 17, 138-146 (1999).
27. Durbin, J. E., Hackenmiller, R., Simon, M. C. & Levy, D. E. Targeted disruption of the mouse Stat1 gene results in compromised innate immunity to viral disease. Cell 84, 443-450 (1996).
28. Meraz, M. A. et al. Targeted disruption of the Stat1 gene in mice reveals unexpected physiologic specificity in the JAK-STAT signaling pathway. Cell 84, 431-442 (1996).
29. Park, C., Li, S., Cha, E. & Schindler, C. Immune response in Stat2 knockout mice. Immunity 13, 795-804 (2000).
30. Kaplan, M. H., Sun, Y. L., Hoey, T. & Grusby, M. J. Impaired IL-12 responses and enhanced development of Th2 cells in Stat4-deficient mice. Nature 382, 174-177 (1996).
31. Shimoda, K. et al. Lack of IL-4-induced Th2 response and IgE class switching in mice with disrupted Stat6 gene. Nature 380, 630-633 (1996).
32. Takeda, K. et al. Essential role of Stat6 in IL-4 signalling. Nature 380, 627-630 (1996).
33. Thierfelder, W. E. et al. Requirement for Stat4 in interleukin-12- mediated responses of natural killer and T cells. Nature 382, 171-174 (1996).
34. Cui, Y. et al. Inactivation of Stat5 in mouse mammary epithelium during pregnancy reveals distinct functions in cell proliferation, survival, and differentiation. Mol. Cell. Biol. 24, 8037-8047 (2004).
35. L induction. Cell 98, 181-191 (1999).
36. Teglund, S. et al. Stat5a and Stat5b proteins have essential and nonessential, or redundant, roles in cytokine responses. Cell 93, 841-850 (1998).
37. Takeda, K. et al. Targeted disruption of the mouse Stat3 gene leads to early embryonic lethality. Proc. Natl Acad. Sci. USA 94, 3801-3804 (1997).
38. Levy, D. E. & Lee, C. K. What does Stat3 do? J. Clin. Invest. 109, 1143-1148 (2002).
39. Horvath, C. M. Silencing STATs: lessons from paramyxovirus interferon evasion. Cytokine Growth Factor Rev. 15, 117-127 (2004).
40. Davis, L. I. The nuclear pore complex. Annu. Rev. Biochem. 64, 865-896 (1995).
41. Rout, M. P. et al. The yeast nuclear pore complex: composition, architecture, and transport mechanism. J. Cell Biol. 148, 635-651 (2000).
42. Suntharalingam, M. & Wente, S. R. Peering through the pore: nuclear pore complex structure, assembly, and function. Dev. Cell 4, 775-789 (2003).
43. Gorlich, D. & Mattaj, I. W. Nucleocytoplasmic transport Science 271, 1513-1518 (1996).
44. Macara, I. G. Transport into and out of the nucleus. Microbiol. Mol. Biol. Rev. 65, 570-594 (2001).
45. Mattaj, I. W. & Englmeier, L. Nucleocytoplasmic transport: the soluble phase. Annu. Rev. Biochem. 67, 265-306 (1998).
46. Pemberton, L. F. & Paschal, B. M. Mechanisms of receptor-mediated nuclear import and nuclear export. Traffic 6, 187-198 (2005). Recent review of nuclear trafficking processes.
47. Bednenko, J., Cingolani, G. & Gerace, L. Nucleocytoplasmic transport: navigating the channel. Traffic 4, 127-135 (2003).
48. Peters, R. Translocation through the nuclear pore complex: selectivity and speed by reduction-of-dimensionality. Traffic 6, 421-427 (2005).
49. Rout, M. P., Aitchison, J. D., Magnasco, M. O. & Chait, B. T. Virtual gating and nuclear transport: the hole picture. Trends Cell Biol. 13, 622-628 (2003).
50. Dingwall, C. & Laskey, R. A. Nuclear targeting sequences - a-consensus? Trends Biochem. Sci. 16, 478-481 (1991).
51. Gorlich, D. & Kutay, U. Transport between the cell nucleus and the cytoplasm. Annu. Rev. Cell Dev. Biol. 15, 607-660 (1999). Comprehensive review of nuclear transport mechanisms.
52. Robbins, J., Dilworth, S. M., Laskey, R. A. & Dingwall, C. Two interdependent basic domains in nucleoplasmin nuclear targeting sequence: identification of a class of bipartite nuclear targeting sequence. Cell 64, 615-623 (1991).
53. Cingolani, G., Petosa, C., Weis, K. & Muller, C. W. Structure of importin-β bound to the IBB domain of importin-α. Nature 399, 221-229 (1999).
54. Conti, E., Uy, M., Leighton, L., Blobel, G. & Kuriyan, J. Crystallographic analysis of the recognition of a nuclear localization signal by the nuclear import factor karyopherin α. Cell 94, 193-204 (1998).
55. Herold, A., Truant, R., Wiegand, H. & Cullen, B. R. Determination of the functional domain organization of the importin α nuclear import factor. J. Cell Biol. 143, 309-318 (1998).
56. Kobe, B. Autoinhibition by an internal nuclear localization signal revealed by the crystal structure of mammalian importin α. Nature Struct. Biol. 6, 388-397 (1999).
57. Kutay, U., Bischoff, F. R., Kostka, S., Kraft, R. & Gorlich, D. Export of importin α from the nucleus is mediated by a specific nuclear transport factor. Cell 90, 1061-1071 (1997).
58. Kohler, M. et al. Evidence for distinct substrate specificities of importin α family members in nuclear protein import. Mol. Cell. Biol. 19, 7782-7791 (1999).
59. Yoneda, Y. Nucleocytoplasmic protein traffic and its significance to cell function. Genes Cells 5, 777-787 (2000).
60. Christophe, D., Christophe-Hobertus, C. & Pichon, B. Nuclear targeting of proteins: how many different signals? Cell. Signal. 12, 337-341 (2000).
61. Strom, A. C. & Weis, K. Importin-β-like nuclear transport receptors. Genome Biol. 2, 3008 (2001).
62. Wen, W., Meinkoth, J. L., Tsien, R. Y. & Taylor, S. S. Identification of a signal for rapid export of proteins from the nucleus. Cell 82, 463-473 (1995).
63. Fornerod, M., Ohno, M., Yoshida, M. & Mattaj, I. W. CRM1 is an export receptor for leucine-rich nuclear export signals. Cell 90, 1051-1060 (1997).
64. Petosa, C. et al. Architecture of CRM1/Exportin1 suggests how cooperativity is achieved during formation of a nuclear export complex. Mol. Cell 16, 761-775 (2004).
65. Kudo, N. et al. Leptomycin B inhibition of signal-mediated nuclear export by direct binding to CRM1. Exp. Cell Res. 242, 540-547 (1998).
66. Wolff, B., Sanglier, J. J. & Wang, Y. Leptomycin B is an inhibitor of nuclear export: inhibition of nucleo- cytoplasmic translocation of the human immunodeficiency virus type 1 (HIV-1) Rev protein and Rev-dependent mRNA. Chem. Biol. 4, 139-147 (1997).
67. Fu, X. Y. A transcription factor with SH2 and SH3 domains is directly activated by an interferon α-induced cytoplasmic protein tyrosine kinase(s). Cell 70, 323-335 (1992).
68. Gutch, M. J., Daly, C. & Reich, N. C. Tyrosine phosphorylation is required for activation of an α interferon-stimulated transcription factor. Proc. Natl Acad. Sci. USA 89, 11411-11415 (1992).
69. Schindler, C., Shuai, K., Prezioso, V. R. & Darnell, J. E., Jr. Interferon-dependent tyrosine phosphorylation of a latent cytoplasmic transcription factor. Science 257, 809-813 (1992).
70. Shuai, K., Stark, G. R., Kerr, I. M. & Darnell, J. E., Jr. A single phosphotyrosine residue of Stat91 required for gene activation by interferon-γ. Science 261, 1744-1746 (1993). References 67-70 demonstrated that direct tyrosine phosphorylation is responsible for STAT activation.
71. Schindler, C., Fu, X. Y., Improta, T., Aebersold, R. & Darnell, J. E., Jr. Proteins of transcription factor ISGF-3: one gene encodes the 91- and 84-kDa ISGF-3 proteins that are activated by interferon α. Proc. Natl Acad. Sci. USA 89, 7836-7839 (1992).
72. Veals, S. A. et al. Subunit of an α-interferon-responsive transcription factor is related to interferon regulatory factor and Myb families of DNA-binding proteins. Mol. Cell. Biol. 12, 3315-3324 (1992).
73. Banninger, G. & Reich, N. C. STAT2 nuclear trafficking. J. Biol. Chem. 279, 39199-39206 (2004). First description of STAT2 nuclear shuttling dependent on a NES in its C terminus and on association with IRF9.
74. Mowen, K. & David, M. Role of the STAT1-SH2 domain and STAT2 in the activation and nuclear translocation of STAT1. J. Biol. Chem. 273, 30073-30076 (1998).
75. Sekimoto, T., Imamoto, N., Nakajima, K., Hirano, T. & Yoneda, Y. 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 (1997). First study to show that importin-α5 specifically recognizes the tyrosine phosphorylated STAT1 dimer.
76. Sekimoto, T., Nakajima, K., Tachibana, T., Hirano, T. & Yoneda, Y. Interferon-γ-dependent nuclear import of Stat1 is mediated by the GTPase activity of Ran/TC4. J. Biol. Chem. 271, 31017-31020 (1996).
77. McBride, K. M., Banninger, G., McDonald, C. & Reich, N. C. Regulated nuclear import of the STAT1 transcription factor by direct binding of importin-α. EMBO J. 21, 1754-1763 (2002). Definitive evidence for a gain-of-function NLS in the DNA-binding domain of STAT1.
78. Melen, K. et al. Importin α nuclear localization signal binding sites for STAT1, STAT2, and influenza A virus nucleoprotein. J. Biol. Chem. 278, 28193-28200 (2003).
79. Melen, K., Kinnunen, L. & Julkunen, I. Arginine/lysine-rich structural element is involved in interferon-induced nuclear import of STATs. J. Biol. Chem. 276, 16447-16455 (2001).
80. Cokol, M., Nair, R. & Rost, B. Finding nuclear localization signals. EMBO Rep. 1, 411-415 (2000).
81. LaCasse, E. C. & Lefebvre, Y. A. Nuclear localization signals overlap DNA- or RNA-binding domains in nucleic acid-binding proteins. Nucleic Acids Res. 23, 1647-1656 (1995).
82. Fagerlund, R., Melen, K., Kinnunen, L. & Julkunen, I. Arginine/lysine-rich nuclear localization signals mediate interactions between dimeric STATs and importin α5. J. Biol. Chem. 277, 30072-30078 (2002).
83. Strehlow, I. & Schindler, C. Amino-terminal signal transducer and activator of transcription (STAT) domains regulate nuclear translocation and STAT deactivation. J. Biol. Chem. 273, 28049-28056 (1998).
84. Subramaniam, P. S., Green, M. M., Larkin, J., Torres, B. A. & Johnson, H. M. Nuclear translocation of IFN-γ is an intrinsic requirement for its biologic activity and can be driven by a heterologous nuclear localization sequence. J. Interferon Cytokine Res. 21, 951-959 (2001).
85. Marg, A. et al. Nucleocytoplasmic shuttling by nucleoporins Nup153 and Nup214 and CRM1-dependent nuclear export control the subcellular distribution of latent Stat1. J. Cell Biol. 165, 823-833 (2004).
86. Meyer, T., Begitt, A., Lodige, I., van Rossum, M. & Vinkemeier, U. Constitutive and IFN-γ-induced nuclear import of STAT1 proceed through independent pathways. EMBO J. 21, 344-354 (2002).
87. Chatterjee-Kishore, M., Wright, K. L., Ting, J. P. & Stark, G. R. How Stat1 mediates constitutive gene expression: a complex of unphosphorylated Stat1 and IRF1 supports transcription of the LMP2 gene. EMBO J. 19, 4111-4122 (2000).
88. Koster, M. & Hauser, H. Dynamic redistribution of STAT1 protein in IFN signaling visualized by GFP fusion proteins. Eur. J. Biochem. 260, 137-144 (1999).
89. Begitt, A., Meyer, T., van Rossum, M. & Vinkemeier, U. Nucleocytoplasmic translocation of Stat1 is regulated by a leucine-rich export signal in the coiled-coil domain. Proc. Natl Acad. Sci. USA 97, 10418-10423 (2000).
90. McBride, K. M., McDonald, C. & Reich, N. C. Nuclear export signal located within the DNA-binding domain of the STAT1 transcription factor. EMBO J. 19, 6196-6206 (2000). Identification of an NES in the DNA-binding domain of STAT1, and evidence that DNA binding is necessary for STAT1 nuclear accumulation.
91. Mowen, K. & David, M. Regulation of STAT1 nuclear export by Jak1. Mol. Cell. Biol. 20, 7273-7281 (2000).
92. Haspel, R. L., Salditt-Georgieff, M. & Darnell, J. E., Jr. The rapid inactivation of nuclear tyrosine phosphorylated Stat1 depends upon a protein tyrosine phosphatase. EMBO J. 15, 6262-6268 (1996).
93. ten Hoeve, J. et al. Identification of a nuclear Stat1 protein tyrosine phosphatase. Mol. Cell. Biol. 22, 5662-5668 (2002). First identification of a nuclear phosphatase that can dephosphorylate STAT1.
94. Shuai, K. & Liu, B. Regulation of gene-activation pathways by PIAS proteins in the immune system. Nature Rev. Immunol. 5, 593-605 (2005).
95. Zhong, M. et al. Implications of an antiparallel dimeric structure of nonphosphorylated STAT1 for the activation-inactivation cycle. Proc. Natl Acad. Sci. USA 102, 3966-3971 (2005).
96. Fu, X. Y., Schindler, C., Improta, T., Aebersold, R. & Darnell, J. E., Jr. The proteins of ISGF-3, the Interferon αlpha-induced transcriptional activator, define a gene family involved in signal transduction. Proc. Natl Acad. Sci. USA 89, 7840-7843 (1992).
97. Lau, J. F., Parisien, J. P. & Horvath, C. M. Interferon regulatory factor subcellular localization is determined by a bipartite nuclear localization signal in the DNA-binding domain and interaction with cytoplasmic retention factors. Proc. Natl Acad. Sci. USA 97, 7278-7283 (2000).
98. Martinez-Moczygemba, M., Gutch, M. J., French, D. L. & Reich, N. C. Distinct STAT structure promotes interaction of STAT2 with the p48 subunit of the interferon-H-stimulated transcription factor ISGF3. J. Biol. Chem. 272, 20070-20076 (1997).
99. Akira, S. et al. Molecular cloning of APRF, a novel IFN-stimulated gene factor 3 p91-related transcription factor involved in the gp130-mediated signaling pathway. Cell 77, 63-71 (1994).
100. Lutticken, C. et al. Association of transcription factor APRF and protein kinase Jak1 with the interleukin-6 signal transducer gp130. Science 263, 89-92 (1994).
101. Wegenka, U. M., Buschmann, J., Lutticken, C., Heinrich, P. C. & Horn, F. Acute-phase response factor, a nuclear factor binding to acute-phase response elements, is rapidly activated by interleukin-6 at the posttranslational level. Mol. Cell. Biol. 13, 276-288 (1993).
102. Zhong, Z., Wen, Z. & Darnell, J. E., Jr. Stat3 and Stat4: members of the family of signal transducers and activators of transcription. Proc. Natl Acad. Sci. USA 91, 4806-4810 (1994).
103. Liu, L., McBride, K. M. & Reich, N. C. STAT3 nuclear import is independent of tyrosine phosphorylation and mediated by importin-α3. Proc. Natl Acad. Sci. USA 102, 8150-8155 (2005). First report showing that importin-α3 is responsible for STAT3 nuclear import independent of tyrosine phosphorylation.
104. Pranada, A. L., Metz, S., Herrmann, A., Heinrich, P. C. & Muller-Newen, G. Real time analysis of STAT3 nucleocytoplasmic shuttling. J. Biol. Chem. 279, 15114-15123 (2004).
105. Kohler, M. et al. Cloning of two novel human importin-α subunits and analysis of the expression pattern of the importin-α protein family. FEBS Lett. 417, 104-108 (1997).
106. Kohler, M., Gorlich, D., Hartmann, E. & Franke, J. Adenoviral E1A protein nuclear import is preferentially mediated by importin α3 in vitro. Virology 289, 186-191 (2001).
107. Welch, K., Franke, J., Kohler, M. & Macara, I. G. RanBP3 contains an unusual nuclear localization signal that is imported preferentially by importin-α3. Mol. Cell. Biol. 19, 8400-8411 (1999).
108. Ma, J. & Cao, X. Regulation of Stat3 nuclear import by importin α5 and importin α7 via two different functional sequence elements. Cell. Signal. 18, 1117-1126 (2005).
109. Ma, J., Zhang, T., Novotny-Diermayr, V., Tan, A. L. & Cao, X. A novel sequence in the coiled-coil domain of Stat3 essential for its nuclear translocation. J. Biol. Chem. 278, 29252-29260 (2003).
110. Yang, J. et al. Novel roles of unphosphorylated STAT3 in oncogenesis and transcriptional regulation. Cancer Res. 65, 939-947 (2005).
111. Ivanov, V. N. et al. Cooperation between STAT3 and c-jun suppresses Fas transcription. Mol. Cell 7, 517-528 (2001).
112. Zhang, X., Wrzeszczynska, M. H., Horvath, C. M. & Darnell, J. E., Jr. Interacting regions in Stat3 and c-Jun that participate in cooperative transcriptional activation. Mol. Cell. Biol. 19, 7138-7146 (1999).
113. Liu, L. et al. Identification of STAT3 as a specific substrate of breast tumor kinase. Oncogene (in the press).
114. Bhattacharya, S. & Schindler, C. Regulation of Stat3 nuclear export. J. Clin. Invest 111, 553-559 (2003).
115. Zeng, R., Aoki, Y., Yoshida, M., Arai, K. & Watanabe, S. Stat5B shuttles between cytoplasm and nucleus in a cytokine-dependent and-independent manner. J. Immunol. 168, 4567-4575 (2002).
116. Herrington, J., Rui, L., Luo, G., Yu-Lee, L. Y. & Carter-Su, C. A functional DNA binding domain is required for growth hormone-induced nuclear accumulation of Stat5B. J. Biol. Chem. 274, 5138-5145 (1999). References 115 and 116 indicate that the nuclear shuttling of STAT5 and its nuclear accumulation depend on DNA binding.
117. Dormann, D., Abe, T., Weijer, C. J. & Williams, J. Inducible nuclear translocation of a STAT protein in Dictyostelium prespore cells: implications for morphogenesis and cell-type regulation. Development 128, 1081-1088 (2001).
118. Fukuzawa, M., Abe, T. & Williams, J. G. The Dictyostelium prestalk cell inducer DIF regulates nuclear accumulation of a STAT protein by controlling its rate of export from the nucleus. Development 130, 797-804 (2003).
119. Hou, S. X., Zheng, Z., Chen, X. & Perrimon, N. The Jak/STAT pathway in model organisms: emerging roles in cell movement. Dev. Cell 3, 765-778 (2002).
120. Kieslinger, M. et al. Antiapoptotic activity of Stat5 required during terminal stages of myeloid differentiation. Genes Dev. 14, 232-244 (2000).
121. Lin, C. C. et al. Characterization of two mosquito STATs, AaSTAT and CtSTAT. Differential regulation of tyrosine phosphorylation and DNA binding activity by lipopolysaccharide treatment and by Japanese encephalitis virus infection. J. Biol. Chem. 279, 3308-3317 (2004).
122. Oates, A. C. et al. Zebrafish stat3 is expressed in restricted tissues during embryogenesis and stat1 rescues cytokine signaling in a STAT1-deficient human cell line. Dev. Dyn. 215, 352-370 (1999).
123. Pascal, A., Riou, J. F., Carron, C., Boucaut, J. C. & Umbhauer, M. Cloning and developmental expression of STAT5 in Xenopus laevis. Mech. Dev. 106, 171-174 (2001).
124. Wang, Y. & Levy, D. E. C. elegans STAT Cooperates with DAF-7TGF-β signaling to repress dauer formation. Curr. Biol. 16, 89-94 (2006).