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. 1997 Jul;17(7):3663–3678. doi: 10.1128/mcb.17.7.3663

Comparison of the transactivation domains of Stat5 and Stat6 in lymphoid cells and mammary epithelial cells.

R Moriggl 1, S Berchtold 1, K Friedrich 1, G J Standke 1, W Kammer 1, M Heim 1, M Wissler 1, E Stöcklin 1, F Gouilleux 1, B Groner 1
PMCID: PMC232218  PMID: 9199300

Abstract

Stat (signal transducers and activators of transcription) and Jak (Janus kinases) proteins are central components in the signal transduction events in hematopoietic and epithelial cells. They are rapidly activated by various cytokines, hormones, and growth factors. Upon ligand binding and cytokine receptor dimerization, Stat proteins are phosphorylated on tyrosine residues by Jak kinases. Activated Stat proteins form homo- or heterodimers, translocate to the nucleus, and induce transcription from responsive genes. Stat5 and Stat6 are transcription factors active in mammary epithelial cells and immune cells. Prolactin activates Stat5, and interleukin-4 (IL-4) activates Stat6. Both cytokines are able to stimulate cell proliferation, differentiation, and survival. We investigated the transactivation potential of Stat6 and found that it is not restricted to lymphocytes. IL-4-dependent activation of Stat6 was also observed in HC11 mammary epithelial cells. In these cells, Stat6 activation led to the induction of the beta-casein gene promoter. The induction of this promoter was confirmed in COS7 cells. The glucocorticoid receptor was able to further enhance IL-4-induced gene transcription through the action of Stat6. Deletion analysis of the carboxyl-terminal region of Stat6 and recombination of this region with a heterologous DNA binding domain allowed the delimitation and characterization of the transactivation domain of Stat6. The potencies of the transactivation domains of Stat5, Stat6, and viral protein VP16 were compared. Stat6 had a transactivation domain which was about 10-fold stronger than that of Stat5. In pre-B cells (Ba/F3), the transactivation domain of Stat6 was IL-4 regulated, independently from its DNA binding function.

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Selected References

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  1. Altiok S., Groner B. Interaction of two sequence-specific single-stranded DNA-binding proteins with an essential region of the beta-casein gene promoter is regulated by lactogenic hormones. Mol Cell Biol. 1993 Dec;13(12):7303–7310. doi: 10.1128/mcb.13.12.7303. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Altiok S., Groner B. beta-Casein mRNA sequesters a single-stranded nucleic acid-binding protein which negatively regulates the beta-casein gene promoter. Mol Cell Biol. 1994 Sep;14(9):6004–6012. doi: 10.1128/mcb.14.9.6004. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Azam M., Erdjument-Bromage H., Kreider B. L., Xia M., Quelle F., Basu R., Saris C., Tempst P., Ihle J. N., Schindler C. Interleukin-3 signals through multiple isoforms of Stat5. EMBO J. 1995 Apr 3;14(7):1402–1411. doi: 10.1002/j.1460-2075.1995.tb07126.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Ball R. K., Friis R. R., Schoenenberger C. A., Doppler W., Groner B. Prolactin regulation of beta-casein gene expression and of a cytosolic 120-kd protein in a cloned mouse mammary epithelial cell line. EMBO J. 1988 Jul;7(7):2089–2095. doi: 10.1002/j.1460-2075.1988.tb03048.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Beadling C., Ng J., Babbage J. W., Cantrell D. A. Interleukin-2 activation of STAT5 requires the convergent action of tyrosine kinases and a serine/threonine kinase pathway distinct from the Raf1/ERK2 MAP kinase pathway. EMBO J. 1996 Apr 15;15(8):1902–1913. [PMC free article] [PubMed] [Google Scholar]
  6. Chi T., Lieberman P., Ellwood K., Carey M. A general mechanism for transcriptional synergy by eukaryotic activators. Nature. 1995 Sep 21;377(6546):254–257. doi: 10.1038/377254a0. [DOI] [PubMed] [Google Scholar]
  7. Delphin S., Stavnezer J. Characterization of an interleukin 4 (IL-4) responsive region in the immunoglobulin heavy chain germline epsilon promoter: regulation by NF-IL-4, a C/EBP family member and NF-kappa B/p50. J Exp Med. 1995 Jan 1;181(1):181–192. doi: 10.1084/jem.181.1.181. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Deutsch H. H., Koettnitz K., Chung J., Kalthoff F. S. Distinct sequence motifs within the cytoplasmic domain of the human IL-4 receptor differentially regulate apoptosis inhibition and cell growth. J Immunol. 1995 Apr 15;154(8):3696–3703. [PubMed] [Google Scholar]
  9. Doppler W., Groner B., Ball R. K. Prolactin and glucocorticoid hormones synergistically induce expression of transfected rat beta-casein gene promoter constructs in a mammary epithelial cell line. Proc Natl Acad Sci U S A. 1989 Jan;86(1):104–108. doi: 10.1073/pnas.86.1.104. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Doppler W., Welte T., Philipp S. CCAAT/enhancer-binding protein isoforms beta and delta are expressed in mammary epithelial cells and bind to multiple sites in the beta-casein gene promoter. J Biol Chem. 1995 Jul 28;270(30):17962–17969. doi: 10.1074/jbc.270.30.17962. [DOI] [PubMed] [Google Scholar]
  11. Dusanter-Fourt I., Muller O., Ziemiecki A., Mayeux P., Drucker B., Djiane J., Wilks A., Harpur A. G., Fischer S., Gisselbrecht S. Identification of JAK protein tyrosine kinases as signaling molecules for prolactin. Functional analysis of prolactin receptor and prolactin-erythropoietin receptor chimera expressed in lymphoid cells. EMBO J. 1994 Jun 1;13(11):2583–2591. doi: 10.1002/j.1460-2075.1994.tb06548.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Gouilleux F., Moritz D., Humar M., Moriggl R., Berchtold S., Groner B. Prolactin and interleukin-2 receptors in T lymphocytes signal through a MGF-STAT5-like transcription factor. Endocrinology. 1995 Dec;136(12):5700–5708. doi: 10.1210/endo.136.12.7588326. [DOI] [PubMed] [Google Scholar]
  13. Gouilleux F., Pallard C., Dusanter-Fourt I., Wakao H., Haldosen L. A., Norstedt G., Levy D., Groner B. Prolactin, growth hormone, erythropoietin and granulocyte-macrophage colony stimulating factor induce MGF-Stat5 DNA binding activity. EMBO J. 1995 May 1;14(9):2005–2013. doi: 10.1002/j.1460-2075.1995.tb07192.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Gouilleux F., Wakao H., Mundt M., Groner B. Prolactin induces phosphorylation of Tyr694 of Stat5 (MGF), a prerequisite for DNA binding and induction of transcription. EMBO J. 1994 Sep 15;13(18):4361–4369. doi: 10.1002/j.1460-2075.1994.tb06756.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Groner B., Altiok S., Meier V. Hormonal regulation of transcription factor activity in mammary epithelial cells. Mol Cell Endocrinol. 1994 Apr;100(1-2):109–114. doi: 10.1016/0303-7207(94)90288-7. [DOI] [PubMed] [Google Scholar]
  16. Groner B., Gouilleux F. Prolactin-mediated gene activation in mammary epithelial cells. Curr Opin Genet Dev. 1995 Oct;5(5):587–594. doi: 10.1016/0959-437x(95)80027-1. [DOI] [PubMed] [Google Scholar]
  17. Grusby M. J., Mitchell S. C., Nabavi N., Glimcher L. H. Casein expression in cytotoxic T lymphocytes. Proc Natl Acad Sci U S A. 1990 Sep;87(17):6897–6901. doi: 10.1073/pnas.87.17.6897. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Harada N., Yang G., Miyajima A., Howard M. Identification of an essential region for growth signal transduction in the cytoplasmic domain of the human interleukin-4 receptor. J Biol Chem. 1992 Nov 15;267(32):22752–22758. [PubMed] [Google Scholar]
  19. Heim M. H., Kerr I. M., Stark G. R., Darnell J. E., Jr Contribution of STAT SH2 groups to specific interferon signaling by the Jak-STAT pathway. Science. 1995 Mar 3;267(5202):1347–1349. doi: 10.1126/science.7871432. [DOI] [PubMed] [Google Scholar]
  20. Heim M. H. The Jak-STAT pathway: specific signal transduction from the cell membrane to the nucleus. Eur J Clin Invest. 1996 Jan;26(1):1–12. doi: 10.1046/j.1365-2362.1996.103248.x. [DOI] [PubMed] [Google Scholar]
  21. Horvath C. M., Wen Z., Darnell J. E., Jr A STAT protein domain that determines DNA sequence recognition suggests a novel DNA-binding domain. Genes Dev. 1995 Apr 15;9(8):984–994. doi: 10.1101/gad.9.8.984. [DOI] [PubMed] [Google Scholar]
  22. 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 Sep 16;265(5179):1701–1706. doi: 10.1126/science.8085155. [DOI] [PubMed] [Google Scholar]
  23. 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 Feb 9;84(3):411–419. doi: 10.1016/s0092-8674(00)81286-6. [DOI] [PubMed] [Google Scholar]
  24. Ihle J. N. STATs: signal transducers and activators of transcription. Cell. 1996 Feb 9;84(3):331–334. doi: 10.1016/s0092-8674(00)81277-5. [DOI] [PubMed] [Google Scholar]
  25. Jacq X., Brou C., Lutz Y., Davidson I., Chambon P., Tora L. Human TAFII30 is present in a distinct TFIID complex and is required for transcriptional activation by the estrogen receptor. Cell. 1994 Oct 7;79(1):107–117. doi: 10.1016/0092-8674(94)90404-9. [DOI] [PubMed] [Google Scholar]
  26. Kammer W., Lischke A., Moriggl R., Groner B., Ziemiecki A., Gurniak C. B., Berg L. J., Friedrich K. Homodimerization of interleukin-4 receptor alpha chain can induce intracellular signaling. J Biol Chem. 1996 Sep 27;271(39):23634–23637. doi: 10.1074/jbc.271.39.23634. [DOI] [PubMed] [Google Scholar]
  27. Kaplan M. H., Schindler U., Smiley S. T., Grusby M. J. Stat6 is required for mediating responses to IL-4 and for development of Th2 cells. Immunity. 1996 Mar;4(3):313–319. doi: 10.1016/s1074-7613(00)80439-2. [DOI] [PubMed] [Google Scholar]
  28. Kaptein A., Paillard V., Saunders M. Dominant negative stat3 mutant inhibits interleukin-6-induced Jak-STAT signal transduction. J Biol Chem. 1996 Mar 15;271(11):5961–5964. doi: 10.1074/jbc.271.11.5961. [DOI] [PubMed] [Google Scholar]
  29. Kazansky A. V., Raught B., Lindsey S. M., Wang Y. F., Rosen J. M. Regulation of mammary gland factor/Stat5a during mammary gland development. Mol Endocrinol. 1995 Nov;9(11):1598–1609. doi: 10.1210/mend.9.11.8584036. [DOI] [PubMed] [Google Scholar]
  30. Kondo M., Takeshita T., Ishii N., Nakamura M., Watanabe S., Arai K., Sugamura K. Sharing of the interleukin-2 (IL-2) receptor gamma chain between receptors for IL-2 and IL-4. Science. 1993 Dec 17;262(5141):1874–1877. doi: 10.1126/science.8266076. [DOI] [PubMed] [Google Scholar]
  31. Kopf M., Le Gros G., Bachmann M., Lamers M. C., Bluethmann H., Köhler G. Disruption of the murine IL-4 gene blocks Th2 cytokine responses. Nature. 1993 Mar 18;362(6417):245–248. doi: 10.1038/362245a0. [DOI] [PubMed] [Google Scholar]
  32. Kotanides H., Reich N. C. Requirement of tyrosine phosphorylation for rapid activation of a DNA binding factor by IL-4. Science. 1993 Nov 19;262(5137):1265–1267. doi: 10.1126/science.7694370. [DOI] [PubMed] [Google Scholar]
  33. Köhler I., Rieber E. P. Allergy-associated I epsilon and Ec epsilon receptor II (CD23b) genes activated via binding of an interleukin-4-induced transcription factor to a novel responsive element. Eur J Immunol. 1993 Dec;23(12):3066–3071. doi: 10.1002/eji.1830231204. [DOI] [PubMed] [Google Scholar]
  34. Kühn R., Rajewsky K., Müller W. Generation and analysis of interleukin-4 deficient mice. Science. 1991 Nov 1;254(5032):707–710. doi: 10.1126/science.1948049. [DOI] [PubMed] [Google Scholar]
  35. Lai S. Y., Xu W., Gaffen S. L., Liu K. D., Longmore G. D., Greene W. C., Goldsmith M. A. The molecular role of the common gamma c subunit in signal transduction reveals functional asymmetry within multimeric cytokine receptor complexes. Proc Natl Acad Sci U S A. 1996 Jan 9;93(1):231–235. doi: 10.1073/pnas.93.1.231. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Lin J. X., Migone T. S., Tsang M., Friedmann M., Weatherbee J. A., Zhou L., Yamauchi A., Bloom E. T., Mietz J., John S. The role of shared receptor motifs and common Stat proteins in the generation of cytokine pleiotropy and redundancy by IL-2, IL-4, IL-7, IL-13, and IL-15. Immunity. 1995 Apr;2(4):331–339. doi: 10.1016/1074-7613(95)90141-8. [DOI] [PubMed] [Google Scholar]
  37. Lischke A., Kammer W., Friedrich K. Different human interleukin-4 mutants preferentially activate human or murine common receptor gamma chain. Eur J Biochem. 1995 Nov 15;234(1):100–107. doi: 10.1111/j.1432-1033.1995.100_c.x. [DOI] [PubMed] [Google Scholar]
  38. 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 U S A. 1995 Sep 12;92(19):8831–8835. doi: 10.1073/pnas.92.19.8831. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Meier V. S., Groner B. The nuclear factor YY1 participates in repression of the beta-casein gene promoter in mammary epithelial cells and is counteracted by mammary gland factor during lactogenic hormone induction. Mol Cell Biol. 1994 Jan;14(1):128–137. doi: 10.1128/mcb.14.1.128. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Mikita T., Campbell D., Wu P., Williamson K., Schindler U. Requirements for interleukin-4-induced gene expression and functional characterization of Stat6. Mol Cell Biol. 1996 Oct;16(10):5811–5820. doi: 10.1128/mcb.16.10.5811. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Moriggl R., Gouilleux-Gruart V., Jähne R., Berchtold S., Gartmann C., Liu X., Hennighausen L., Sotiropoulos A., Groner B., Gouilleux F. Deletion of the carboxyl-terminal transactivation domain of MGF-Stat5 results in sustained DNA binding and a dominant negative phenotype. Mol Cell Biol. 1996 Oct;16(10):5691–5700. doi: 10.1128/mcb.16.10.5691. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Mosley B., Beckmann M. P., March C. J., Idzerda R. L., Gimpel S. D., VandenBos T., Friend D., Alpert A., Anderson D., Jackson J. The murine interleukin-4 receptor: molecular cloning and characterization of secreted and membrane bound forms. Cell. 1989 Oct 20;59(2):335–348. doi: 10.1016/0092-8674(89)90295-x. [DOI] [PubMed] [Google Scholar]
  43. Mosmann T. R., Sad S. The expanding universe of T-cell subsets: Th1, Th2 and more. Immunol Today. 1996 Mar;17(3):138–146. doi: 10.1016/0167-5699(96)80606-2. [DOI] [PubMed] [Google Scholar]
  44. Mui A. L., Wakao H., Kinoshita T., Kitamura T., Miyajima A. Suppression of interleukin-3-induced gene expression by a C-terminal truncated Stat5: role of Stat5 in proliferation. EMBO J. 1996 May 15;15(10):2425–2433. [PMC free article] [PubMed] [Google Scholar]
  45. Quelle F. W., Shimoda K., Thierfelder W., Fischer C., Kim A., Ruben S. M., Cleveland J. L., Pierce J. H., Keegan A. D., Nelms K. Cloning of murine Stat6 and human Stat6, Stat proteins that are tyrosine phosphorylated in responses to IL-4 and IL-3 but are not required for mitogenesis. Mol Cell Biol. 1995 Jun;15(6):3336–3343. doi: 10.1128/mcb.15.6.3336. [DOI] [PMC free article] [PubMed] [Google Scholar]
  46. Qureshi S. A., Leung S., Kerr I. M., Stark G. R., Darnell J. E., Jr Function of Stat2 protein in transcriptional activation by alpha interferon. Mol Cell Biol. 1996 Jan;16(1):288–293. doi: 10.1128/mcb.16.1.288. [DOI] [PMC free article] [PubMed] [Google Scholar]
  47. Raught B., Liao W. S., Rosen J. M. Developmentally and hormonally regulated CCAAT/enhancer-binding protein isoforms influence beta-casein gene expression. Mol Endocrinol. 1995 Sep;9(9):1223–1232. doi: 10.1210/mend.9.9.7491114. [DOI] [PubMed] [Google Scholar]
  48. Ripperger J. A., Fritz S., Richter K., Hocke G. M., Lottspeich F., Fey G. H. Transcription factors Stat3 and Stat5b are present in rat liver nuclei late in an acute phase response and bind interleukin-6 response elements. J Biol Chem. 1995 Dec 15;270(50):29998–30006. doi: 10.1074/jbc.270.50.29998. [DOI] [PubMed] [Google Scholar]
  49. Russell S. M., Keegan A. D., Harada N., Nakamura Y., Noguchi M., Leland P., Friedmann M. C., Miyajima A., Puri R. K., Paul W. E. Interleukin-2 receptor gamma chain: a functional component of the interleukin-4 receptor. Science. 1993 Dec 17;262(5141):1880–1883. doi: 10.1126/science.8266078. [DOI] [PubMed] [Google Scholar]
  50. Ryan J. J., McReynolds L. J., Keegan A., Wang L. H., Garfein E., Rothman P., Nelms K., Paul W. E. Growth and gene expression are predominantly controlled by distinct regions of the human IL-4 receptor. Immunity. 1996 Feb;4(2):123–132. doi: 10.1016/s1074-7613(00)80677-9. [DOI] [PubMed] [Google Scholar]
  51. Sad S., Marcotte R., Mosmann T. R. Cytokine-induced differentiation of precursor mouse CD8+ T cells into cytotoxic CD8+ T cells secreting Th1 or Th2 cytokines. Immunity. 1995 Mar;2(3):271–279. doi: 10.1016/1074-7613(95)90051-9. [DOI] [PubMed] [Google Scholar]
  52. Sadowski I., Ma J., Triezenberg S., Ptashne M. GAL4-VP16 is an unusually potent transcriptional activator. Nature. 1988 Oct 6;335(6190):563–564. doi: 10.1038/335563a0. [DOI] [PubMed] [Google Scholar]
  53. Saito H., Oka T. Hormonally regulated double- and single-stranded DNA-binding complexes involved in mouse beta-casein gene transcription. J Biol Chem. 1996 Apr 12;271(15):8911–8918. doi: 10.1074/jbc.271.15.8911. [DOI] [PubMed] [Google Scholar]
  54. Schaefer T. S., Sanders L. K., Nathans D. Cooperative transcriptional activity of Jun and Stat3 beta, a short form of Stat3. Proc Natl Acad Sci U S A. 1995 Sep 26;92(20):9097–9101. doi: 10.1073/pnas.92.20.9097. [DOI] [PMC free article] [PubMed] [Google Scholar]
  55. Schindler C., Darnell J. E., Jr Transcriptional responses to polypeptide ligands: the JAK-STAT pathway. Annu Rev Biochem. 1995;64:621–651. doi: 10.1146/annurev.bi.64.070195.003201. [DOI] [PubMed] [Google Scholar]
  56. 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 alpha. Proc Natl Acad Sci U S A. 1992 Aug 15;89(16):7836–7839. doi: 10.1073/pnas.89.16.7836. [DOI] [PMC free article] [PubMed] [Google Scholar]
  57. Schindler C., Kashleva H., Pernis A., Pine R., Rothman P. STF-IL-4: a novel IL-4-induced signal transducing factor. EMBO J. 1994 Mar 15;13(6):1350–1356. doi: 10.1002/j.1460-2075.1994.tb06388.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  58. Schindler U., Wu P., Rothe M., Brasseur M., McKnight S. L. Components of a Stat recognition code: evidence for two layers of molecular selectivity. Immunity. 1995 Jun;2(6):689–697. doi: 10.1016/1074-7613(95)90013-6. [DOI] [PubMed] [Google Scholar]
  59. Schmitt-Ney M., Doppler W., Ball R. K., Groner B. Beta-casein gene promoter activity is regulated by the hormone-mediated relief of transcriptional repression and a mammary-gland-specific nuclear factor. Mol Cell Biol. 1991 Jul;11(7):3745–3755. doi: 10.1128/mcb.11.7.3745. [DOI] [PMC free article] [PubMed] [Google Scholar]
  60. Schmitt-Ney M., Happ B., Ball R. K., Groner B. Developmental and environmental regulation of a mammary gland-specific nuclear factor essential for transcription of the gene encoding beta-casein. Proc Natl Acad Sci U S A. 1992 Apr 1;89(7):3130–3134. doi: 10.1073/pnas.89.7.3130. [DOI] [PMC free article] [PubMed] [Google Scholar]
  61. Seder R. A., Paul W. E. Acquisition of lymphokine-producing phenotype by CD4+ T cells. Annu Rev Immunol. 1994;12:635–673. doi: 10.1146/annurev.iy.12.040194.003223. [DOI] [PubMed] [Google Scholar]
  62. Shimoda K., van Deursen J., Sangster M. Y., Sarawar S. R., Carson R. T., Tripp R. A., Chu C., Quelle F. W., Nosaka T., Vignali D. A. Lack of IL-4-induced Th2 response and IgE class switching in mice with disrupted Stat6 gene. Nature. 1996 Apr 18;380(6575):630–633. doi: 10.1038/380630a0. [DOI] [PubMed] [Google Scholar]
  63. Standke G. J., Meier V. S., Groner B. Mammary gland factor activated by prolactin on mammary epithelial cells and acute-phase response factor activated by interleukin-6 in liver cells share DNA binding and transactivation potential. Mol Endocrinol. 1994 Apr;8(4):469–477. doi: 10.1210/mend.8.4.7519723. [DOI] [PubMed] [Google Scholar]
  64. Stöcklin E., Wissler M., Gouilleux F., Groner B. Functional interactions between Stat5 and the glucocorticoid receptor. Nature. 1996 Oct 24;383(6602):726–728. doi: 10.1038/383726a0. [DOI] [PubMed] [Google Scholar]
  65. Takeda K., Tanaka T., Shi W., Matsumoto M., Minami M., Kashiwamura S., Nakanishi K., Yoshida N., Kishimoto T., Akira S. Essential role of Stat6 in IL-4 signalling. Nature. 1996 Apr 18;380(6575):627–630. doi: 10.1038/380627a0. [DOI] [PubMed] [Google Scholar]
  66. Tepper R. I., Levinson D. A., Stanger B. Z., Campos-Torres J., Abbas A. K., Leder P. IL-4 induces allergic-like inflammatory disease and alters T cell development in transgenic mice. Cell. 1990 Aug 10;62(3):457–467. doi: 10.1016/0092-8674(90)90011-3. [DOI] [PubMed] [Google Scholar]
  67. 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 May 1;13(9):2182–2191. doi: 10.1002/j.1460-2075.1994.tb06495.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  68. Wang H. Y., Paul W. E., Keegan A. D. IL-4 function can be transferred to the IL-2 receptor by tyrosine containing sequences found in the IL-4 receptor alpha chain. Immunity. 1996 Feb;4(2):113–121. doi: 10.1016/s1074-7613(00)80676-7. [DOI] [PubMed] [Google Scholar]
  69. Wartmann M., Cella N., Hofer P., Groner B., Liu X., Hennighausen L., Hynes N. E. Lactogenic hormone activation of Stat5 and transcription of the beta-casein gene in mammary epithelial cells is independent of p42 ERK2 mitogen-activated protein kinase activity. J Biol Chem. 1996 Dec 13;271(50):31863–31868. doi: 10.1074/jbc.271.50.31863. [DOI] [PubMed] [Google Scholar]
  70. Wen Z., Zhong Z., Darnell J. E., Jr Maximal activation of transcription by Stat1 and Stat3 requires both tyrosine and serine phosphorylation. Cell. 1995 Jul 28;82(2):241–250. doi: 10.1016/0092-8674(95)90311-9. [DOI] [PubMed] [Google Scholar]
  71. Wery S., Letourneur M., Bertoglio J., Pierre J. Interleukin-4 induces activation of mitogen-activated protein kinase and phosphorylation of shc in human keratinocytes. J Biol Chem. 1996 Apr 12;271(15):8529–8532. doi: 10.1074/jbc.271.15.8529. [DOI] [PubMed] [Google Scholar]
  72. Yan R., Small S., Desplan C., Dearolf C. R., Darnell J. E., Jr Identification of a Stat gene that functions in Drosophila development. Cell. 1996 Feb 9;84(3):421–430. doi: 10.1016/s0092-8674(00)81287-8. [DOI] [PubMed] [Google Scholar]
  73. Yoshimura A., Ichihara M., Kinjyo I., Moriyama M., Copeland N. G., Gilbert D. J., Jenkins N. A., Hara T., Miyajima A. Mouse oncostatin M: an immediate early gene induced by multiple cytokines through the JAK-STAT5 pathway. EMBO J. 1996 Mar 1;15(5):1055–1063. [PMC free article] [PubMed] [Google Scholar]
  74. Yoshimura A., Ohkubo T., Kiguchi T., Jenkins N. A., Gilbert D. J., Copeland N. G., Hara T., Miyajima A. A novel cytokine-inducible gene CIS encodes an SH2-containing protein that binds to tyrosine-phosphorylated interleukin 3 and erythropoietin receptors. EMBO J. 1995 Jun 15;14(12):2816–2826. doi: 10.1002/j.1460-2075.1995.tb07281.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  75. Yu-Lee L. Y., Hrachovy J. A., Stevens A. M., Schwarz L. A. Interferon-regulatory factor 1 is an immediate-early gene under transcriptional regulation by prolactin in Nb2 T cells. Mol Cell Biol. 1990 Jun;10(6):3087–3094. doi: 10.1128/mcb.10.6.3087. [DOI] [PMC free article] [PubMed] [Google Scholar]
  76. Zhang X., Blenis J., Li H. C., Schindler C., Chen-Kiang S. Requirement of serine phosphorylation for formation of STAT-promoter complexes. Science. 1995 Mar 31;267(5206):1990–1994. doi: 10.1126/science.7701321. [DOI] [PubMed] [Google Scholar]

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