STAT6: Its role in interleukin 4-mediated biological functions

Journal of Molecular Medicine

Volumn 75, Issue 5, 1997, Pages 317-326

  Takeda, Kiyoshi ^a,b   Kishimoto, Tadamitsu ^a   Akira, Shizuo ^a,b  

^a OSAKA UNIVERSITY MEDICAL SCHOOL   (Japan)

^b HYOGO COLLEGE OF MEDICINE   (Japan)

Author keywords

IL4 induced phototyrosine substrate insulin receptor substrate; interleukin 13; interleukin 4; signal transducer and activator of transcription 6; signal transduction

Indexed keywords

INTERLEUKIN 4; TRANSCRIPTION FACTOR;

GENE CONTROL; HUMAN; IMMUNE RESPONSE; REVIEW; SIGNAL TRANSDUCTION; TRANSCRIPTION REGULATION;

ANIMALS; ANTIGENS, CD; HUMANS; INTERLEUKIN-13; INTERLEUKIN-4; RECEPTORS, INTERLEUKIN; RECEPTORS, INTERLEUKIN-4; SIGNAL TRANSDUCTION; STAT6 TRANSCRIPTION FACTOR; TRANS-ACTIVATORS;

EID: 0030949167     PISSN: 09462716     EISSN: None     Source Type: Journal    
DOI: 10.1007/s001090050117     Document Type: Review

References (120)

1. Howard M, Farrar J, Hilfiker M, Johnson B, Takatsu K, Hamaoka T, Paul WE (1982) Identification of a T cell-derived B cell growth factor distinct from interleukin 2. J Exp Med 155:914-923
2. Plaut M, Pierce JH, Watson CJ, Hanley-Hyde J, Nordan RP, Paul WE (1989) Mast cell lines produce lymphokine in response to cross-linkage of FcεRI or to calcium ionophores. Nature 339:64-67
3. Seder RA, Paul WE, Dvorak AM, Sharkis SJ, Kagey-Sobotka A, Niv Y, Finkelman FD, Barbieri SA, Galli SJ, Plaut M (1991) Mouse splenic and bone marrow cell populations that express high-affinity Fcε receptors and produce interleukin-4 are highly enriched in basophils. Proc Natl Acad Sci USA 88:2835-2839
4. Paul WE (1991) Interleukin-4: a prototypic immunoregulatory lymphokine. Blood 77:1859-1870
5. Noelle R, Krammer PH, Ohara J, Uhr JW, Vitetta E (1984) Increased expression of Ia antigens on resting B cells: additional role of B-cell growth factor. Proc Natl Acad Sci USA 81:6149-6153
6. Roem NW, Leibson HJ, Zlotonik A, Kappler J, Marrack P, Cambier JC (1984) Interleukin-induced increase in Ia expression by normal mouse B cells. J Exp Med 160:679-694
7. Conrad DH, Keegan AD, Kalli KR, Dusen RV, Rao M, Levine AD (1988) Superinduction of low affinity IgE receptors on murine B lymphocytes by lipopolysaccharide and IL-4. J Immunol 141:1091-1097
8. Keegan AD, Snapper CM, Dusen RV, Paul WE, Conrad DH (1989) Superinduction of the murine B cell FcεRII by T helper cell clones: role of IL-4. J Immunol 142:3868-3874
9. Coffman RL, Lebman DA, Rothman P (1993) Mechanism and regulation of immunoglobulin isotype switching. Adv Immunol 54:229-270
10. Finkelman FD, Katona I, Urban J, Snapper C, Ohara J, Paul WE (1986) Suppression of in vivo polyclonal IgE responses by monoclonal antibody to the lymphokine BSF-1. Proc Natl Acad Sci USA 83:9765-9768
11. Finkelman FD, Holmes J, Katona IM, Urban J, Beckmann MP, Park LS, Schooley KA, Coffman RL, Mossmann TR (1990) Lymphokine control of in vivo immunoglobulin isotype selection. Annu Rev Immunol 8:303-333
12. Kühn R, Rajewsky K, Müller W (1991) Generation and analysis of interleukin-4 deficient mice. Science 254:707-710
13. Kopf M, Gros GL, Bachmann M, Lamers MC, Bluthmann H, Köhler G (1993) Disruption of the murine IL-4 gene blocks Th2 cytokine responses. Nature 362:245-248
14. Keegan AD, Nelms K, Wang LM, Pierce JH, Paul WE (1994) Interleukin 4 receptor: signaling mechanisms. Immunol Today 15:423-432
15. Mosley B, Beckmann MP, March CJ, Idzerda RL, Gimpel SD, Van den Bos T, Friend D, Alpert A, Anderson D, Jackson J, Wignall JM, Smith C, Gallis B, Sims JE, Urdal D, Widmer MB, Cosman D, Park LS (1989) The murine interleukin-4 receptor: molecular cloning and characterization of secreted and membrane bound forms. Cell 59:335-348
16. Idzerda RL, March CJ, Mosley B, Lynman SD, Van den Bos T, Gimpel SD, Din WS, Grabstein K, Widmer MB, Park LS, Cosman D, Beckmann MP (1990) Human interleukin 4 receptor confers biological responsiveness and defines a novel receptor superfamily. J Exp Med 171:861-873
17. Galizzi JP, Zuber CE, Harada N, Gorman DM, Djossou O, Kastelein R, Banchereau J, Howard M, Miyajima A (1990) Molecular cloning of a cDNA encoding the human interleukin-4 receptor. Int Immunol 2:669-675
18. Bazan JF (1990) Structural design and molecular evolution of a cytokine receptor superfamily. Proc Natl Acad Sci USA 87:6934-6938
19. Murakami M, Narazaki M, Hibi M, Yawata H, Yasukawa K, Hamaguchi M, Taga T, Kishimoto T (1991) Critical cytoplasmic region of the IL-6 signal transducer, gp130, is conserved in the cytokine receptor family. Proc Natl Acad Sci USA 88:11349-11353
20. Fukunaga R, Ishizaka-Ikeda E, Pan CX, Seto Y, Nagata S (1991) Functional domains of the granulocyte colony-stimulating factor receptor. EMBO J 10:2855-2865
21. Keegan AD, Nelms K, White M, Wang LM, Pierce JH, Paul WE (1994) An IL-4 receptor region containing an insulin receptor motif is important for IL-4-mediated IRS-1 phosphorylation and cell growth. Cell 76:811-820
22. Seldin DC, Leder P (1994) Mutational analysis of a critical signaling domain of the human interleukin 4 receptor. Proc Natl Acad Sci USA 91:2140-2144
23. Harada N, Yang G, Miyajima A, Howard M (1994) Identification of an essential region for growth signal transduction in the cytoplasmic domain of the human interleukin-4 receptor. J Biol Chem 267:22752-22758
24. Takeshita T, Asao H, Ohtani K, Ishii N, Kumaki S, Tanaka N, Munakata H, Nakamura M, Sugamura K (1992) Cloning of the γ chain of the human IL-2 receptor. Science 257:379-382
25. Russel SM, Keegan AD, Harada N, Nakamura Y, Noguchi M, Leland P, Friedmann MC, Miyajima A, Puri RK, Paul WE, Leonard WJ (1993) Interleukin-2 receptor γ chain: a functional component of the interleukin-4 receptor. Science 262:1880-1883
26. Noguchi N, Nakamura Y, Russel SM, Ziegler SF, Tsang M, Cao X, Leonard WJ (1993) Interleukin-2 receptor γ chain: a functional component of the interleukin-7 rceptor. Science 262:1877-1880
27. Kondo M, Takeshita T, Higuchi M, Nakamura M, Sudo T, Nishikawa S, Sugamura K (1994) Functional participation of the IL-2 receptor γ chain in IL-7 receptor complexes. Science 263:1453-1454
28. Russel SM, Johnston JA, Noguchi M, Kawamura M, Bacon CM, Friedmann M, Berg M, McVicar DW, Witthuhn BA, SiIvennoinen O, Goldman AS, Schmalsteig FC, Ihle JN, O'Shea JJ, Leonard WJ (1994) Interaction of IL-2Rβ and γc chains with Jak1 and Jak3: Implications for XSCID and SCID. Science 266:1042-1045
29. Giri JG, Ahdieh M, Eisenman J, Shanebeck K, Grabstein K, Kumaki S, Namen A, Park LS, Cosman D, Anderson D (1994) Utilization of the β and γ chains of the IL-2 receptor by the novel cytokine IL-15. EMBO J 13:2822-2830
30. Noguchi M, Yi H, Rosenblatt HM, Filipovich AH, Adelstein S, Modi WS, McBride OW, Leonard WJ (1993) Interleukin-2 receptor γ chain mutation results in X-linked-severe combined immunodeficiency in humans. Cell 73:147-157
31. Cao X, Shores EW, Hu-Ki J, Anver MR, Keisall BL, Russell SM, Drago J, Noguchi M, Grinberg A, Bloom ET, Paul WE, Kats SI, Love PE, Leonard WJ (1995) Defective lymphoid development in mice lacking expression of the common cytokine receptor γ chain. Immunity 2:223-238
32. DiSanto JP, Müller W, Guy-Grand D, Fischer A, Rajewsky K (1995) Lymphoid development in mice with a targeted disruption of the interleukin 2 receptor γ chain. Proc Natl Acad Sci USA 92:377-381
33. Sugamura K, Asao H, Kondo M, Tanaka N, Ishii N, Ohbo K, Nakamura M, Takeshita T (1996) The interleukin-2 receptor γ chain: its role in the multiple cytokine receptor complexes and T cell development in XSCID. Annu Rev Immunol 14:179-205
34. Taniguchi T (1995) Cytokine signaling through nonreceptor protein tyrosine kinases. Science 268:251-255
35. lck: identification of novel intermolecular association. Science 252:1523-1528
36. lyn with the interleukin 2 receptor: implication for redunduncy and pleiotropism in cytokine signal transduction. Proc Natl Acad Sci USA 90:4201-4205
37. Argetsinger LS, Campbell GS, Yang X, Witthuhn BA, Si-Ivennoinen O, Ihle JN, Carter-Su C (1993) Identification of JAK2 as a growth hormone receptor-associated tyrosine kinase. Cell 74:237-244
38. Witthuhn BA, Quelle FW, Silvennoinen O, Yi T, Tang B, Miura O, Ihle JN (1993) JAK2 associates with the erythropoietin receptor and is tyrosine phosphorylated and activated following stimulation with erythropoietin. Cell 74:227-236
39. Narazaki M, Witthuhn BA, Yoshida K, Silvennoinen O, Yasukawa K, Ihle JN, Kishimoto T, Taga T (1994) Activation of JAK2 kinase mediated by the interleukin 6 siganal transducer gp130. Proc Natl Acad Sci USA 91:2285-2289
40. Yin T, Tsang ML, Yang YC (1994) JAK1 kinase forms complexes with interleukin-4 receptor and 4PS/insulin receptor substrate-1-like protein and is activated by interleukin-4 and interleukin-9 in T lymphocytes. J Biol Chem 269:26614-26617
41. Miyazaki T, Kawahara A, Fujii H, Nakagawa Y, Minami Y, Lui ZJ, Oishi I, Silvennoinen O, Witthuhn BA, Ihle JN, Taniguchi T (1994) Functional activation of Jak1 and Jak3 by selective association with IL-2 receptor subunits. Science 266:1045-1047
42. Schindler C, Darnell Jr JE (1995) Transcriptional responses to polypeptide ligands: the JAK-STAT pathway. Annu Rev Biochem 64:621-651
43. Wang LM, Keegan AD, Paul WE, Heidaran MA, Gutkind S, Pierce JH (1992) IL-4 activates a distinct signal transduction cascade from IL-3 in factor-dependent myeloid cells. EMBO J 11:4899-4908
44. Sun XJ, Wang LM, Zhang Y, Yenush L, Myers MG, Glasheen E, Wolf G, Shoelson SE, Lane WS, Pierce JH, White MF (1995) Role of IRS2 in insulin and cytokine signaling. Nature 377:173-177
45. Wang LM, Keegan AD, Li W, Lienhard GE, Pacini S, Gutkind JS, Myers MG, Sun XJ, White MF, Aaronson SA, Paul WE, Pierce JH (1993) Common elements in interleukin-4 and insulin signaling pathways in factor-dependent hematopoietic cells. Proc Natl Acad Sci USA 90:4032-4036
46. Sun XJ, Rothenberg P, Kahn CR, Backer JM, Araki E, Wilden PA, Cahill DA, Goldstein BJ, White MF (1991) Structure of the insulin receptor substrate IRS-1 defines a unique signal transduction protein. Nature 352:73-77
47. He W, O'Neill TJ, Gustafson TA (1995) Distinct modes of interaction of SHC and insulin receptor substrate-1 with the insulin receptor NPEY region via non-SH2 domains. J Biol Chem 270:23258-23262
48. Wolf G, Trüb T, Ottinger E, Groninga L, Lynch A, White M Miyazaki M, Lee J, Shoelson SE (1995) The PTB domains of IRS-1 and She have distinct but overlapping binding specificities. J Biol Chem 270:27407-27410
49. Backer JM, Kahn CR, Cachill DA, Ullrich A, White MF (1990) Receptor mediated internalization of insulin requires a 12-amino acid sequence in the juxtamembrane region of the insulin receptor β-subunit. J Biol Chem 265:16450-16454
50. Skolnik EY, Lee CH, Batzer A, Vicetini LM, Zhou M, Daly R, Myers Jr MJ, Backer JM, Ullrich A, White MF, Schlessinger J (1993) The SH2/SH3 domain-containing protein GRB2 interacts with tyrosine-phosphorylated IRS-1 and Shc: implications for insulin control of ras signaling. EMBO J 12:1929-1936
51. Freeman RM, Plutzky J, Neel BG (1992) Identification of a human src homology 2-containing protein-tyrosine-phosphatase: a putative homolog of Drosophila corkskrew. Proc Natl Acad Sci USA 89:11239-11243
52. Wang LM, Myers MG, Sun XJ, Aaronson SA, White M, Pierce JH (1993) IRS1: essential for insulin- and IL-4-stimulated mitogenesis in hematopoietic cells. Science 261:1591-1594
53. O'Neill TJ, Craparo A, Gustafson TA (1994) Characterization of an interaction between insulin receptor substrate 1 and the insulin receptor by using the two-hybrid system. Mol Cell Biol 14:6433-6442
54. Kotanides H, Reich NC (1993) Requirement of tyrosine phosphorylation for rapid activation of a DNA binding factor by IL-4. Science 262:1265-1267
55. Schindler C, Kashleva H, Pernis A, Pine R, Rothman P (1994) STF-IL-4: a novel IL-4-induced signal transducing factor. EMBO J 13:1350-1356
56. Hou J, Schindler U, Henzel WJ, Ho TC, Brasseur M, McKnight SL (1994) An interleukin-4-induced transcription factor: IL-4 Stat. Science 265:1701-1706
57. Levy DE, Kessler DS, Pine R, Reich N, Darnell Jr JE (1988) Interferon-induced nuclear factors that bind a shared promoter element correlate with positive and negative transcriptional control Genes Dev 2:383-393
58. Levy DE, Kessler DS, Pine RI, Darnell Jr JE (1989) Cytoplasmic activation of ISGF3, the positive regulator of interferon-alpha-stimulated transcroption, reconstituted in vitro. Genes Dev 3:1362-1372
59. Decker T, Lew DJ, Mirkovitch J, Darnell Jr JE (1991) Cytoplasmic activation of GAF, an IFN γ-regulated DNA-binding factor. EMBO J 10:927-932
60. Lew D, Decker T, Strehlow I, Darnell Jr JE (1991) Overlapping elements in the Guanylate-binding protein gene promoter mediate transcriptional induction by alpha and gamma interferons. Mol Cell Biol 11:182-191
61. Fu XY, Kessler DS, Veals SA, Levy DE, Darnell Jr JE (1990) ISGF3, the transcriptional activator induced by interferon alpha, consists of multiple interacting polypeptide chains. Proc Natl Acad Sci USA 87:8555-8559
62. Fu XY, Schindler C, Improta T, Aebersold R, Darnell Jr JE (1992) The proteins of ISGF-3, the interferon α-induced transcriptional activator, define a gene family involved in signal transduction. Proc Natl Acad Sci USA 89:7840-7843
63. Veals SA, Schindler C, Leonard D, Fu XY, Aebersold R, Darnell Jr JE, Levy DE (1992) Subunit of an alpha interferon-responsive transcription factor is related to interferon regulatory factor and Myb families of DNA binding proteins. Mol Cell Biol 12:3315-3324
64. Schindler C, Fu XY, Improta T, Aebersold R, Darnell Jr JE (1992) 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
65. Kessler DS, Veals SA, Fu XY, Levy DE (1990) Interferon-alpha regulates nuclear translocation and DNA-binding affinity of ISGF3, a multimeric transcriptional activator. Genes Dev 4:1753-1765
66. Schindler C, Shuai K, Prezioso VR, Darnell Jr JE (1992) Interferon dependent tyrosine phosphorylation of a latent cytoplasmic transcription factor. Science 257:809-815
67. Akira S, Nishio Y, Inoue M, Wang XJ, Wei S, Matsusaka T, Yoshida K, Sudo T, Naruto M, Kishimoto T (1994) Molecular cloning of APRF, a novel ISGF3 p91-related transcription factor involved in the gp130-mediated signaling pathway. Cell 77:63-71
68. Zhong Z, Wen Z, Darnell Jr JE (1994) Stat3: a Stat family member activated by tyrosine phosphorylation in response to epidermal growth factor and interleukin-6. Science 264:95-98
69. Yamamoto K, Quelle FW, Thierfelder WE, Kreider BI, Gilbert DJ, Jenkins NA, Copeland NG, Silvennoinen O, Ihle JN (1994) STAT4, a novel γ interferon activation site binding protein expressed in early myeloid differentiation. Mol Cell Biol 14:4342-4349
70. Wakao H, Gouilleux F, Groner B (1994) Mammary gland factor (MGF) is a novel member of the cytokine regulated transcription factor gene family and confers the prolactin response. EMBO J 13:2182-2191
71. Darnell Jr JE, Kerr IM, Stark GR (1994) Jak-STAT pathways and transcriptional activation in response to IFNs and other extracellular signaling proteins. Science 264:1415-1421
72. Ihle JN, Witthuhn BA, Quelle FW, Tamamoto K, Thierfelder WE, Kreider B, Silvennoinen O (1994) Signaling by the cytokine receptor superfamily: JAKs and STATs. Trends Biochem Sci 19:222-227
73. Ihle JN, Kerr IM (1995) Jaks and STATs in signaling by the cytokine receptor superfamily. Trends Genet 11:69-75
74. Ihle JN (1995) Cytokine receptor signaling. Nature 377:591-594
75. Heim MH, Kerr IM, Stark GR, Darnell Jr JE (1995) Contribution of STAT SH groups to specific interferon signaling by the Jak-STAT pathway. Science 267:1347-1349
76. Stahl N, Farruggell TJ, Boulton TG, Zhong Z, Darnell Jr JE, Yancopoulos GD (1995) Choice of STATs and other substrates specified by modular tyrosine-based motifs in cytokine receptors. Science 267:1349-1353
77. Minami M, Inoue M, Wei S, Takeda K, Matsumoto M, Kishimoto T, Akira S (1996) STAT3 activation is a critical step in gp130-mediated terminal differentiation and growth arrest of a myeloid cell line. Proc Natl Acad Sci USA 93:3963-3966
78. Yamanaka Y, Nakajima K, Fukada T, Hibi M, Hirano T (1996) Differentiation and growth arrest signals are generated through the cytoplasmic region of gp130 that is essential for Stat3 activation. EMBO J 15:1557-1565
79. Quelle FW, Shimoda K, Thierfelder W, Fischer C, Kim A, Ruben SN, Cleveland JL, Pierce JH, Keegan AD, Nelms K, Paul WE, Ihle JN (1995) Cloning of murine Stat6 and human Stat6. Stat proteins that are tyrosine phosphorylated in response to IL-4 and IL-3 but are not required for mitogenesis. Mol Cell Biol 15:3336-3343
80. Ihle JN (1996) STATs: signal transducers and activators of transcription. Cell 84:331-334
81. Fujii H, Nakagawa Y, Schindler U, Kawahara A, Mori H, Gouilleux F, Groner B, Ihle JN, Minami Y, Miyazaki T, Taniguchi T (1995) Activation of Stat5 by interleukin 2 requires a carboxy-terminal region of the interleukin 2 receptor β chain but is not essential for the proliferative signal transduction. Proc Natl Acad Sci USA 92:5482-5486
82. Danial NN, Pernis A, Rothman PB (1995) Jak-STAT signaling induced by the v-abl oncogene. Science 269:1875-1877
83. Migone TS, Lin JX, Cereseto A, Mulloy JC, O'shea JJ, Franchini G, Leonard WJ (1995) Constitutively activated Jak-STAT pathway in T cells transformed with HTLV-1. Science 269:79-81
84. Yu CL, Meyer DJ, Campbell GS, Larner AC, Carter-Su C, Schwartz J, Jove R (1995) Enhanced DNA-binding activity of a Stat3-related protein in cells transformed by the Src oncoprotein. Science 269:81-83
85. WAF1/CIP1 mediated by STAT1. Science 272:719-722
86. Damen JE, Wakao H, Miyajima A, Krosl J, Humphries RK, Cutler RL, Krystal G (1995) Tyrosine 343 in the erythropoietin receptor positively regulates erythropoietin-induced cell proliferation and Stat5 activation. EMBO J 14:5557-5568
87. Gobert S, Chresien S, Gouilleux F, Muller O, Pallad C, Dusanter-Fourt I, Groner B, Lacombe C, Gisselbrecht S, Mayeux P (1996) Identification of tyrosine residues within the intracellular domain of the erythropoietin receptor crucial for STAT5 activation. EMBO J 15:2434-2441
88. Mui AL, Wakao H, Kinoshita T, Kiatamura T, Miyajima A (1996) Suppression of interleukin-3-induced gene expression by a C-terminal truncated STAT5: role of STATS in proliferation. EMBO J 15:2425-2433
89. Larner AC, David M, Feldman GM, Igarashi K, Hackett RH, Webb DSA, Sweitzer SM, Petricoin EF, Finbloom DS (1993) Tyrosine phosphorylation of DNA binding proteins by multiple cytokines. Science 261:1730-1733
90. Finbloom DS, Winestock KD (1995) IL-10 induces the tyrosine phosphorylation of Tyk2 and JAK1 and the differential assembly of STAT1α and STAT3 complexes in human T cells and monocytes. J Immunol 155:1079-1090
91. Wen Z, Zhong Z, Darnell Jr JE (1995) Maximal activation of transcription by Stat1 and Stat3 requires both tyrosine and serine phosphorylation. Cell 82:241-250
92. Gronowski AM, Zhong Z, Wen Z, Thomas MJ, Darnell Jr JE (1995) In vivo growth hormone treatment rapidly stimulates the tyrosine phosphorylation and activation of Stat3. Mol Endocrinol 9:171-177
93. Bhat GJ, Thekkumkara TJ, Thomas WG, Conrad KM, Baker KM (1994) Angiotensin II stimulates sis-inducing factor-like DNA binding activity: evidence that the AT1A receptor activates transcription factor-Stat91 and/or a related protein. J Biol Chem 269:31443-31449
94. Gurney AL, Wong SC, Henzel WJ, de Sauvage FJ (1995) Distinct regions of C-Mpl cytoplasmic domain are coupled to the JAK-STAT signal transduction pathway and Shc phosphorylation. Proc Natl Acad Sci USA 92:5292-5296
95. Meraz MA, White JM, Sheehan KCF, Bach EA, Rodig SJ, Dighe AS, Kaplan DH, Riley JK, Greenland AC, Campbell D, Carver-Moore K, DuBois RN, Clark R, Aguet M, Schreiber RD (1996) Targeted disruption of Stat1 gene in mice reveals unexpected physiologic specificity in the JAK STAT signaling pathway. Cell 84:431-142
96. Durbin JE, Hackenmiller R, Simon MC, Levy DE (1996) Targeted disruption of the mouse Stat1 gene results in compromised innate immunity to viral disease. Cell 84:443-450
97. Takeda K, Tanaka T, Shi W, Matsumoto M, Minami M, Kashiwamura S, Nakanishi K, Yoshida N, Kishimoto T, Akira S (1996) Essential role of Stat6 in IL-4 signaling. Nature 380:627-630
98. Shimoda K, Deursen J, Sangster MY, Sarawar SR, Carson RT, Tripp RA, Chu C, Quelle FW, Nosaka T, Vignali DAA, Doherty PC, Grosveld G, Paul WE, Ihle JN (1996) Lack of IL-4-induced Th2 response and IgE class switching in mice with disrupted Stat6 gene. Nature 380:630-633
99. Kaplan MH, Schindler U, Smiley ST, Grusby MJ (1996) Stat6 is required for mediating responses to IL-4 and for the development of Th2 cells. Immunity 4:313-319
100. Romagnani S (1994) Lymphokine production by human T cells in disease states. Annu Rev Immunol 12:227-257
101. + T cells. Annu Rev Immunol 12:635-673
102. Thierfelder WE, van Deursen J, Yamamoto K, Tripp RA, Sarawar SR, Carson RT, Sangster MY, Vignali DAA, Doherty PC, Grosveld GC, Ihle JN (1996) Requirement for Stat4 in interleukin-12-mediated responses of natural killer and T cells. Nature 382:171-174
103. Kaplan MH, Sun Y, Hoey T, Grusby MJ (1996) Impaired IL-12 responses and enhanced development of Th2 cells in Stat4-deficient mice. Nature 382:174-177
104. Minty A, Charon P, Derocq JM, Dumont X, Guillemot JC, Kaghad M, Labit C, Leplatois P, Liauzun P, Miloux B, Minty C, Casellas P, Loison G, Lupker J, Shire D, Ferrara P, Caput D (1993) Inlerleukin-13 is a new human lymphokine regulating inflammatory and immune responses. Nature 362:248-250
105. Zurawski G, de Vries JE (1994) Interleukin 13, an interleukin 4-like cytokine that acts on monocytes and B cells, but not on T cells. Immunol Today 15:19-26
106. Punnonen J, Aversa G, Cocks BG, McKenzie ANJ, Menon S, Zurawski G, de Waal Malefyt R, de Vries JE (1993) Interleukin 13 induces interluekin 4-independent IgG4 and IgE synthesis and CD23 expression by human B cells. Proc Natl Acad Sci USA 90:3730-3734
107. McKenzie ANJ, Culpepper JA, de Waal Malefyt R, Briere F, Punnonen J, Aversa G, Sato A, Dang W, Cocks BG, Menon S, de Vries JE, Banchereau J, Zurawski G (1993) Interleukin 13, a T-cell-derived cytokine that regulates human monocyte and B-cell function. Proc Natl Acad Sci USA 90:3735-3739
108. Matthews DJ, Clark PA, Herbert J, Morgan G, Armitage RJ, Kinnon C, Minty C, Grabstein KH, Caput D, Callard R (1995) Function of the interleukin-2 (IL-2) receptor γ-chain in biologic responses of X-linked severe combined immunodeficient B cells to IL-2, IL-4, IL-13, and IL-15. Blood 85:38-42
109. Zurawski SM, Chormarat P, Djossou O, Bidaud C, McKenzie ANJ, Missec P, Banchereau J, Zurawski G (1995) The primary binding subunit of the human interleukin-4 receptor is also a component of the interleukin 13 receptor. J Biol Chem 270:13869-13878
110. Lin XJ, Migone TS, Tsang M, Friedmann M, Weatherbee JA, Zhou L, Yamauchi A, Bloom ET, Mietz J, John S, Leonard WJ (1995) The role of shared receptor motifs and common Stat proteins in the generation of cytokine pleiotropy and redunduncy by IL-2, IL-4, IL-7, IL-13, and IL15. Immunity 2:331-339
111. Hillon DJ, Zhang JG, Metcalf D, Alexander WS, Nicola NA, Willson TA (1996) Cloning and characterization of a binding subunit of the interleukin 13 receptor that is also a component of the interleukin 4 receptor. Proc Natl Acad Sci USA 93:497-501
112. Doherty TM, Kastelein R, Menon S, Andrade S, Coffman RL (1993) Modulation of murine macrophage function by IL-13. J Immunol 151:7151-7160
113. de Waal Malefyt R, Figdor CG, Huijbens R, Mohan-Peterson S, Bennett B, Culpepper J, Dang W, Zurawski G, de Vries JE (1993) Effects of IL-13 on phenotype, cytokine production, and cytotoxic function of human monocytes. Comparison with IL-4 and modulation by IFN-γ or IL-10. J Immunol 151:6370-6381
114. Sakamoto O, Hashiyama M, Minty A, Ando M, Suda T (1995) Interleukin-13 selectively suppresses the growth of human macrophage progenitors at the late stage. Blood 85:3487-3493
115. Takeda K, Kamanaka M, Tanaka T, Kishimoto T, Akira S (1996) Impaired IL-13-mediated functions of macrophages in STAT6-deficient mice. J Immunol 157:3220-3223
116. Heinzel FP, Sadick MD, Holaday BJ, Coffman RL, Locksley RM (1989) Reciprocal expression of interferon γ or interleukin 4 during the regulation or progression of murine leishmaniasis. J Exp Med 169:59-72
117. + lymphocytes in vivo during healing and progressive murine leishmaniasis. Proc Natl Acad Sci USA 88:7011-7015
118. + effector cells default to the Th2 pathway in interferon γ-deficient mice infected with Leishmania major. J Exp Med 179:1367-1371
119. Reiner SL, Locksley RM (1995) The regulation of immunolgy to Leishmania major. Annu Rev Immunol 13:151-177
120. Noben-Trauth N, Kropf P, Müller I (1996) Susceptibility to Leishmania major infection in interleukin-4-deficient mice. Science 271:987-990