Signal transduction via the interleukin-4 receptor and its correlation with atopy (Review)

International Journal of Molecular Medicine

Volumn 3, Issue 1, 1999, Pages 3-10

  Izuhara, Kenji ^a   Shirakawa, Taro ^b  

^a KYUSHU UNIVERSITY   (Japan)

^b SWANSEA UNIVERSITY   (United Kingdom)

Author keywords

Allergy; Atopy; IgE; Interieukin 4 receptor chain; Interleukin 4

Indexed keywords

INTERLEUKIN 13; INTERLEUKIN 4; INTERLEUKIN 4 RECEPTOR;

GENETICS; HUMAN; IMMEDIATE TYPE HYPERSENSITIVITY; PATHOPHYSIOLOGY; PHYSIOLOGY; REVIEW; SIGNAL TRANSDUCTION;

HUMANS; HYPERSENSITIVITY, IMMEDIATE; INTERLEUKIN-13; INTERLEUKIN-4; RECEPTORS, INTERLEUKIN-4; SIGNAL TRANSDUCTION;

EID: 0032622175     PISSN: 11073756     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Article

References (107)

1. Coffman RL, Lebman DA and Rothman P: Mechanism and regulation of immunoglobulin isotype switching. Adv Immunol 54: 229-270, 1993.
2. Snapper CM, Marcu KB and Zelazowski P: The immunoglobulin class switch: beyond 'accessibility'. Immunity 6: 217-223, 1997.
3. Coca AF and Cooke RA: On the classification of the phenomena of hypersensitiveness. J Immunol 8: 163-182, 1923.
4. Mao X-Q, Shirakawa T, Yoshikawa K, Kawai M, Sasaki S, Enomoto T, Hashimoto T, Furuyama J, Hopkin JM and Morimoto K: Association between genetic variants of mast-cell chymase and eczema. Lancet 348: 581-583, 1996.
5. Shirakawa T, Enomoto T, Shimazu S and Hopkin JM: The inverse association between tuberculin responses and atopic disorder. Science 275: 77-79, 1997.
6. Barnes KG and Marsh DG: The genetics and complexity of allergy and asthma. Immunol Today 19: 325-332, 1998.
7. Cookson WOCM: Genetics, atopy and asthma. Allergol Int 45: 3-11, 1996.
8. Daniels SE, Bhattacharrya S, James A, Leaves NI, Young A, Hill MR, Faux JA, Ryan GF, Le Soüef PN, Lathrop GM, Musk AW and Cookson WOCM: A genome-wide search for quantitative trait loci underlying asthma. Nature 383: 247-250, 1996.
9. Deichmann KA, Heinzmann A, Forster J, Dischinger S, Mehl C, Brueggenolte E, Hildebrandt F, Moseler M and Kuehr J: Linkage and allelic association of atopy and markers flanking the IL4-rcceptor gene. Clin Exp Allergy 28: 151-155, 1998.
10. Cookson WOCM, Sharp PA, Faux JA and Hopkin JM: Linkage between immunoglobulin E responses underlying asthma and rhinitis and chromosome 11q. Lancet 1: 1292-1295, 1989.
11. Shirakawa T, Hashimoto T, Furuyama J, Takeshita T and Morimoto K: Linkage between severe atopy and chromosome 11q13 in Japanese families. Clin Genet 46: 228-232, 1994.
12. Folster-Holst R, Moises HW, Yang L, Fritsch W, Weissenbach J and Christophers E: Linkage between atopy and the IgE high-affinity receptor gene at 11q13 in atopic dermatitis families. Hum Genet 102: 236-239, 1998.
13. Collee JM, ten Kate LP, de Vries HG, Kliphuis JW, Bouman K, Scheffer H and Gerritscn J: Allele sharing on chromosome 11q13 in sibs with asthma and atopy. Lancet 342: 936, 1993.
14. Cookson WOCM, Young RP, Sandford AJ, Moffatt MF, Shirakawa T, Sharp PA, Faux JA, Julier C, Le Soüef PN, Nakamura Y, Lathrop GM and Hopkin JM: Maternal inheritance of atopic IgE responsiveness on chromosome 11q. Lancet 340: 381-384, 1992.
15. Sandford AJ, Shirakawa T, Moffatt MF, Daniels SE, Ra C, Faux JA, Young RP, Nakamura Y, Lathrop GM, Cookson WOCM and Hopkin JM: Localisation of atopy and β subunit of high-affinity IgE receptor (FcεRI) on chromosome llq. Lancet 341: 332-334, 1993.
16. Shirakawa T, Li A, Dubowitz M, Dekkcr JW, Shaw AE, Faux JA, Ra C, Cookson WOCM and Hopkin JM: Association between atopy and variants of the β subunit of the high-affinity immunoglobulin E receptor. Nat Genet 7: 125-129, 1994.
17. Hill MR, James AL, Faux JA, Ryan G, Hopkin JM, Le Soüef P, Musk AW and Cookson WOCM: FcεRI-β polymorphism and risk of atopy in a general population sample. Br Med J 311: 776-779, 1995.
18. Hill MR and Cookson WOCM: A new variant of the β subunit of the high-affinity receptor for immunoglobulin E (FcεRI-β E237G): associations with measures of atopy and bronchial hyperresponsiveness. Hum Mol Genet 5: 959-962, 1996.
19. Shirakawa T, Mao X-Q, Sasaki S, Enomoto T, Kawai M, Morimoto K and Hopkin JM: Association between atopic asthma and a coding variant of FcεRIβ in a Japanese population. Hum Mol Genet 5: 1129-1130, 1996.
20. Palmer LJ, Pare PD, Faux JA, Moffatt MF, Daniels SE, le Soüef PN, Bremner PR, Mockford E, Gracey M, Spargo R, Musk AW and Cookson WOCM: FcεRI-β polymorphism and total serum IgE levels in endemically parasitized Australian aborigines. Am J Hum Genet 61: 182-188, 1997.
21. Shirakawa T, Mao X-Q, Sasaki S, Kawai M, Morimoto K and Hopkin JM: Association between FcεRIβ and atopic disorder in a Japanese population. Lancet 347: 394-395, 1996.
22. Mao X-Q, Shirakawa T, Sasaki S, Enomoto T, Morimoto K and Hopkin JM: Maternal inheritance of atopy at the FcεRIβ locus in Japanese sibs. Hum Hered 47: 178-180, 1996.
23. Cox HE, Moffatt MF, Faux JA, Walley AJ, Coleman R, Trembath RC, Cookson WOCM and Harper JI: Association of atopic dermatitis to the β subunit of the high affinity immunoglobulin E receptor. Br J Dermatol 138: 182-187, 1998.
24. Hijazi Z, Haider MZ, Khan MR and Al-Dowaisan AA: High frequency of IgE receptor FcεRIβ variant (Leu181/Leu183) in Kuwaiti Arabs and its association with asthma. Clin Genet 53: 149-152, 1998.
25. Trabetti E, Cusin V, Malcrba G, Martinati LC, Casartelli A, Boner AL and Pignatti PF: Association of the FcεRIβ gene with bronchial hyper-responsiveness in an Italian population J Med Genet 35: 680-681, 1998.
26. Green S, Gaillard MC, Song E, Dewar JB and Halks A: Polymorphisms of the β chain of the high affinity immunoglobulin E receptor (FcεRIβ) in South African black and white asthmatic and non-asthmatic individuals. Am J Respir Crit Care Med (In press).
27. Li A, Mackay GA and Hopkin JM: Functional analysis of histamine release from basophils and mast cells in subjects with the Ile-181→Leu variant of FcεRI-β. Clin Sci 93: 279-286, 1997.
28. Lin S, Cicala C, Scharenberg AM and Kinet JP: The FcεRI-β subunit functions as an amplifier of FcεRIγ-mediated cell activation signals. Cell 85: 985-995, 1996.
29. Dombrowicz D, Lin S, Flamand V, Brini AT, Koller BH and Kinet JP: Allergy-associated FcRβ is a molecular amplifier of IgE- and IgG-mediated in vivo responses. Immunity 8: 517-529, 1998.
30. Marsh DG, Neely JD, Breazeale DR, Ghosh B, Freidhoff LR, Ehrlich-Kautzky E, Schou C, Krishnaswamy G and Beaty TH: Linkage analysis of IL4 and other chromosome 5q31.1 markers and total serum immunoglobulin E concentrations. Science 264: 1152-1156, 1994.
31. Postma DS, Bleecker ER, Amelung PJ, Holroyd KJ, Xu J, Panhuysen CI, Meyers DA and Levitt RC: Genetic susceptibility to asthma-bronchial hyperresponsiveness coinherited with a major gene for atopy. N Engl J Med 333: 894-900, 1995.
32. Noguchi E, Shibasaki M, Arinami T, Takeda K, Maki T, Miyamoto T, Kawashima T, Kobayashi K and Hamaguchi H: Evidence for linkage between asthma/atopy in childhood and chromosome 5q31-q33 in a Japanese population. Am J Respir Crit Care Med 156: 1390-1393, 1997.
33. Ulbrecht M, Eisenhut T, Bonisch J, Kruse R, Wjst M, Heinrich J, Wichmann HE, Weiss EH and Albert ED: High serum IgE concentrations: association with HLA-DR and markers on chromosome 5q31 and chromosome 11q13. J Allergy Clin Immunol 99: 828-836, 1997.
34. Doull IJ, Lawrence S, Watson M, Begishvili T, Beasley RW, Lampe F, Holgate T and Morton NE: Allelic association of gene markers on chromosomes 5q and 11q with atopy and bronchial hyperresponsiveness. Am J Respir Crit Care Med 153: 1280-1284, 1996.
35. Rosenwasser LJ and Borish L: Genetics of atopy and asthma: the rationale behind promoter-based candidate gene studies (IL-4 and IL-10). Am J Respir Crit Care Med 156: S152-S155, 1997.
36. Pereira E, Goldblatt J, Rye P, Sanderson C and Le Soüef P: Mutation analysis of interleukin-5 in an asthmatic cohort. Hum Mutat 11: 51-54, 1998.
37. Laitinen T, Kauppi P, Ignatius J, Ruotsalainen T, Daly MJ, Kaariainen H, Kruglyak L, Laitinen H, de la Chapelle A, Lander ES, Laitinen LA and Kere J: Genetic control of serum IgE levels and asthma: linkage and linkage disequilibrium studies in an isolated population. Hum Mol Genet 6: 2069-2076, 1997.
38. Barnes KC, Neely JD, Duffy DL, Freidhoff LR, Breazeale DR, Schou C, Naidu RP, Levett PN, Renault B, Kucherlapati R, lozzino S, Ehrlich E, Beaty TH and Marsh DG: Linkage of asthma and total serum IgE concentration to markers on chromosome 12q: evidence from Afro-Caribbean and Caucasian populations. Genomics 37: 41-50, 1996.
39. Andre F, Pene J and Andre C: Interleukin-4 and interferon-γ production by peripheral blood mononuclear cells from food-allergic patients. Allergy 51: 350-355, 1996.
40. Pociot F, Veijola R, Johannesen J, Hansen PM, Lorenzen T, Karlsen AE, Reijonen H, Knip M and Nerup J: Analysis of an interferon-γ gene (IFNγ) polymorphism in Danish and Finnish insulin-dependent diabetes mellitus (IDDM) patients and control subjects. Danish Study Group of Diabetes in Childhood. J Interferon Cytokine Res 17: 87-93, 1997.
41. Paul WE: Interleukin-4: a prototypic immunoregulatory lymphokine. Blood 77: 1859-1870, 1991.
42. Zurawski G and de Vries JE: Interleukin 13, an interleukin 4-like cytokine that acts on monocytes and B cells, but not on T cells. Immunol Today 15: 19-26, 1994.
43. Gauchat JF, Schlagenhauf E, Feng NP, Moser R, Yamage M, Jeannin P, Alouani S, Elson G, Notarangelo LD, Wells T, Eugster HP and Bonnefoy JY: A novel 4-kb interleukin-13 receptor a mRNA expressed in human B, T, and endothelial cells encoding an alternate type-II interleukin-4/interleukin-13 receptor. Eur J Immunol 27: 971-978, 1997.
44. Bancroft AJ, McKenzie ANJ and Grencis RK: A critical role for IL-13 in resistence to intestinal nematode infection. J Immunol 160: 3453-3461, 1998.
45. McKenzie GJ, Emson CL, Bell SE, Anderson S, Fallon P, Zurawski G, Murray R, Grencis R and McKenzie ANJ: Impaired development of Th2 cells in IL-I3-deficient mice. Immunity 9: 423-432, 1998.
46. Kishimoto T, Taea T and Akira S: Cytokine sianal transduction. Cell 76: 253-2627, 1994.
47. Leonard WJ, Shores EW and Love PE: Role of the common cytokinc receptor y chain in cytokine signaling and lymphoid development. Immunol Rev 148: 97-114, 1995.
48. Aman MJ, Tayebi N, Obiri NI, Puri RK, Modi WS and Leonard WJ: cDNA cloning and characterization of the human interleukin 13 receptorn a chain. J Biol Chem 271: 29265-29270, 1996.
49. Murata T, Taguchi J and Puri RK: Interleukin-13 receptor a' but not a chain: a functional component of interleukin-4 receptors. Blood 91: 3884-3891, 1998.
50. Lai SY, Molden J, Liu KD, Puck JM, White MD and Goldsmith MA: Interleukin-4-specific signal transduction events are driven by homotypic interactions of the interleukin-4 receptor a subunit. EMBOJ 15: 4506-4514, 1996.
51. Fujiwara H, Hanissian SH, Tsytsykova A and Geha RS: Homodimerization of the human interleukin 4 receptor α chain induces CE germline transcripts in B cells in the absence of the interleukin 2 receptor γ chain. Proc Natl Acad Sci USA 94: 5866-5871, 1997.
52. Reichel M, Nelson BH, Greenberg PD and Rothman PB: The IL-4 receptor α-chain cytoplasmic domain is sufficient for activation of JAK-1 and STAT6 and the induction of IL-4-specific gene expression. J Immunol 158: 5860-5867, 1997.
53. Izuhara K, Heike T, Otsuka T, Yamaoka K, Mayumi M, Imamura T, Niho Y and Harada N: Signal transduction pathway of interleukin-4 and interleukin-13 in human B cells derived from X-linked severe combined immunodeficiency patients. J Biol Chem 271: 619-622, 1996.
54. Taylor N, Candotti F, Smith S, Oakes SA, Jahn T, Isakov J, Puck JM, O'Shea JJ, Weinberg K and Johnston JA: Interleukin-4 signaling in B lymphocytes from patients with X-linked severe combined immunodeficiency. J Biol Chem 272: 7314-7319, 1997.
55. Moriggl R, Erhardt I, Kammer W and Berchtold S: Activation of STAT6 is not dependent on phosphotyrosine-mediated docking to the interleukin-4 receptor and can be blocked by dominantnegative mutants of both receptor subunits. Eur J Biochem 251: 25-35, 1998.
56. Caput D, Laurent P, Kaghad M, Lelias J-M, Lefort S, Vita N and Ferrara P: Cloning and characterization of a specific interleukin (IL)-13 binding protein structurally related to the IL-5 receptor a chain. J Biol Chem 271: 16921-16926, 1996.
57. Schindler C and Darnell JE Jr: Transcriptional responces to polypeptide ligands: the JAK-STAT pathway. Annu Rev Biochem 64: 621-651, 1995.
58. Ihle JN: Cytokine receptor signaling. Nature 377: 591-594, 1995.
59. Lin J-X, Migone T-S, Tsang M, Friedmann M, Weatherbee JA, Zhou L, Yamauchi A, Bloom ET, Mietz J, John S and Leonard WJ: 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 2: 331-339, 1995.
60. Welham MJ, Learmonth L, Bone H and Schrader JW: Interleukin-13 signal transduction in lymphohemopoietic cells: similarities and differences in signal transduction with interleukin-4 and insulin. J Biol Chem 270: 12286-12296, 1995.
61. Orchansky PL, Ayrcs SD, Hilton DJ and Schrader JW: An interleukin (IL)-13 receptor lacking the cytoplasmic domain fails to transduce IL-13-induced signals and inhibits response to IL-4. J Biol Chem 272: 22940-22947, 1997.
62. Takeda K, Tanaka T, Shi W, Matsumoto M, Minami M, Kashiwamura S, Nakanishi K, Yoshida N, Kishimoto T and Akira S: Essential role of State in IL-4 signalinc. Nature 380: 627-630, 1996.
63. Shimoda K, van Deursen J, Sangster MY, Sarawar SR, Carson RT, Tripp RA, Chu C, Quelle FW, Nosaka T, Vignali DAA, Doherty PC, Grosveld G, Paul WE and Ihle JN: Lack of IL-4-induced Th2 response and IgE class switching in mice with disrupted Stato gene. Nature 380: 630-633, 1996.
64. Kaplan MH, Schindler U, Smiley ST and Grusby MJ: Stato is required for mediating responses to IL-4 and for development of Th2 cells. Immunity 4: 313-319, 1996.
65. Delphin S and Stavnezer J: Characterization of an interleukin 4 (IL-4) responsive region in the immunoglobulin heavy chain germline E promoter: regulation by NF-IL-4, a C/EBP family member and NF-κB/p50. J Exp Med 181: 181-192, 1995.
66. Mikita T, Campbell D, Wu P, Williamson K and Schindler U: Requirements for intcrIeukin-4-induccd gene expression and functional characterization of Stato. Mol Cell Biol 16: 5811-5820, 1996.
67. Takeda K, Kamanaka M, Tanaka T, Kishimoto T and Akira S: Impaired IL-13-mediated functions of macrophages in STAT6-deficient mice. J Imniunol 157: 3220-3222, 1996.
68. Ichiki T, Takahashi W and Watanabe T: Regulation of the expression of human Cε germline transcript. J Immunol 150: 5408-5417, 1993.
69. Thienes CP, De Monte L, Monticelli S, Busslinger M, Gould HJ and Vercelli D: The transcription factor B cell-specific activator protein (BSAP) enhances both IL-4- and CD40-mediated activation of the human E germline promoter. J Immunol 158: 5874-5882, 1997.
70. Messner B, Stütz AM, Albrecht B, Peiritsch S and Woisetschläger M: Cooperation of binding sites for STAT6 and NFκB/rel in the IL-4-induccd up-regulation of the human IgE germline promoter. J Immunol 159: 3330-3337, 1997.
71. Shen C-H and Stavnezer J: Interaction of Stato and NF-κB: direct association and synergistic activation of interleukin-4-induced transcription. Mol Cell Biol 18: 3395-3404, 1998.
72. Yanagihara Y, Basaki Y, Ikizawa K and Kajiwara K: Possible role of nuclear factor-κB activity in germline CE transcription in a human Burkitt lymphoma B cell line. Cell Immunol 176: 66-74, 1997.
73. Wang L-M, Keegan AD, Paul WE, Heidaran MA, Gutkind JS and Pierce.JH: IL-4 activates a distinct signal transduction cascade from IL-3 in factor-dependent myeloid cells. EMBO J 11: 4899-4908, 1992.
74. Izuhara K and Harada N: Interleukin-4 (IL-4) induces protein tyrosine phosphorylation of the IL-4 receptor and association of phosphatidylinositol 3-kinase to the IL-4 receptor in a mouse T cell line, HT2. J Biol Chem 268: 13097-13102, 1993.
75. Sun XJ, Wang L-M, Zhang Y, Yenush L, Myers MG Jr, Glasheen E, Lane WS, Pierce JH and White MF: Role of IRS-2 in insulin and cytokine signalling. Nature 377: 173-177, 1995.
76. Johnston JA, Wang L-M, Hanson EP, Sun X-J, White MF, Oakes SA, Pierce JH and O'Shea JJ: Interleukin 2, 4, 7, and 15 stimulate tyrosine phosphorylation of insulin receptor substrate 1 and 2 in T cells. J Biol Chem 270: 28527-28530, 1995.
77. Wang HY, Zamorano J, Yoerkie JL, Paul WE and Keegan AD: The IL-4-induced tyrosine phosphorylation of the insulin receptor substrate is dependent on JAK1 expression in human fibrosarcoma cells. J Immunol 158: 1037-1040, 1997.
78. Chen XH, Patel BK, Wang LM, Frankel M, Ellmore N, Flavell RA, LaRochelle WJ and Pierce JH: Jakl expression is required for mediating interleukin-4-induced tyrosine phosphorylation of insulin receptor substrate and Stato signaling molecules. J Biol Chem 272: 6556-6560, 1997.
79. Keegan AD, Johnston JA, Tortolani PJ, McReynolds LJ, Kinzer C, O'Shea JJ arid Paul WE: Similarities and differences in signal transduction by interleukin 4 and interleukin 13: analysis of Janus kinase activation. Proc Natl Acad Sci USA 92: 7681-7685, 1995.
80. Ikizawa K, Kajiwara K, Basaki Y, Koshio T and Yanagihara Y: Evidence for a role of phosphatidylinositol 3-kinasc in IL-4-induced germline CE transcription. Cell Immunol 170: 134-140, 1996.
81. Wang L-M, Myers MG Jr, Sun X-J, Aaronson SA, White M and Pierce JH: IRS-1: essential for insulin- and IL-4-stimulated mitogenesis in hematopoietic cells. Science 261: 1591-1594, 1993.
82. Izuhara K, Feldman RA, GreerP and Harada N: Interaction of the c-fes proto-oncogene product with the interleukin-4 receptor. J Biol Chem 269: 18623-18629, 1994.
83. Izuhara K, Feldman RA, Greer P and Harada N: Interleukin-4 induces association of the c-fes proto-oncogenc product with phosphatidylinositol-3 kinase. Blood 88: 3910-3918, 1996.
84. Izuhara K and Harada N: Interleukin-4 activates two distinct pathways of phosphatidylinositol-3 kinase in the same cells. Biochem Biophys Res Commun 229: 624-629, 1996.
85. Miyajima A, Kitamura T, Harada N, Yokota T and Aral K: Cytokine receptors and signal transduction. Annu Rev Immunol 10: 295-331, 1992.
86. Murakami M, Narazaki M, Hibi M, Yawata H, Yasukawa K, Hamaguchi M, Taga T and Kishimoto T: Critical cytoplasmic region of the interleukin 6 signal transducer gp130 is conserved in the cytokine receptor family. Proc Natl Acad Sci USA 88: 11349-11353, 1991.
87. Harada N, Yang G, Miyajima A and Howard M: Identification of an essential region for growth signal transduction in the cyto-plasmic domain of the human interleukin-4 receptor. J Biol Chem 267: 22752-22758, 1992.
88. Kammer W, Lischke A, Moriggl R, Groner B, Ziemiecki A, Gurniak CB, Berg LJ and Friedrich K: Homodimerization of interlcukin-4 reccjitor a chain can induce intracellular signaling. J Biol Chem 271: 23634-23637, 1996.
89. Harada N, Higuchi K, Wakao H, Hamasaki N and Izuhara K: Identification of the critical portions of'the human IL-4 receptor α chain for activation of STAT6. Biochem Biophys Res Commun 246: 675-680, 1998.
90. Ihle JN, Witthuhn BA, Quelle FW, Yamamoto K and Silvennoinen O: Signaling through the hematopoietic cytokine receptors. Annu Rev Immunol 13: 369-398, 1995.
91. Seldin DC and Leder P: Mutational analysis of a critical signaling domain of the human intcrleukin 4 receptor. Proc Natl Acad Sci US A 91: 2140-2144, 1994.
92. Schultz C, Izuhara K, Coffman R and Harada N: The critical region in the cytoplasmic domain of human IL-4 receptor for induction of IgE synthesis. Immunol Lett 46: 215-219, 1995.
93. Kecgan AD, Nelms K, White M, Wang L-M, Pierce JH and Paul WE: 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, 1994.
94. Quelle FW, Shimoda K, Thierfelder W, Fischer C, Kim A, Ruben SM, Cleveland JL, Pierce JH, Keegan AD, Nelms K, Paul WE and Ihle JN: Cloning of murine Stato and human Stato, Slat 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, 1995.
95. Pemis A, Witthuhn B, Keegan AD, Nelms K, Garfein E, Ihle JN, Paul WE, Pierce JH and Rothman P: Interleukin 4 signals through two related pathways. Proc Natl Acad Sci USA 92: 7971-7975, 1995.
96. Wang HY, Paul WE and Keegan AD: IL-4 function can be trans-ferred to the IL-2 receptor by tyrosine containing sequences found in the IL-4 receptor a chain. Immunity 4: 113-121, 1996.
97. Zamorano J, Wang HY, Wang L-M, Pierce JH and Keegan AD: IL-4 protects cells from apoptosis via the insulin receptor substrate pathway and a second independent signaling pathway. J Immunol 157: 4926-4934, 1996.
98. Hou J, Schindler U, Henzel WJ, Ho TC, Brasseur M and McKnight SL: An interleukin-4-induced transcription factor: IL-4 Stat. Science 265: 1701-1706, 1994.
99. Ryan JJ, McReynolds LJ, Keegan A, Wang L-H, Garfein E, Rothman P, Nelms K and Paul WE: Growth and gene expression are predominantly controlled by distinct regions of the human IL-4 receptor. Immunity 4: 123-132, 1996.
100. Khurana Hershey GK, Friedrich MF, Esswein LA, Thomas ML and Chatila TA: The association of atopy with a gain-offunction mutation in the a subunit of the intcrleukin-4 receptor. N Engl J Med 337: 1720-1725, 1997.
101. Schulte T, Kurrle R, Röllinghoff M and Gessner A: Molecular characterization and functional analysis of murine interleukin 4 receptor allotypes. J Exp Med 186: 1419-1429, 1997.
102. Idzerda RL, March CJ, Mosley B, Lyman SD, Vanden Bos T, Gimpel SD, Din WS, Grabstein K, Widmer MB, Park LS, Cosman D and Backmann MP: Human interleukin 4 receptor confers biological responsiveness and defines a novel receptor superfamily. J Exp Med 171: 861-873, 1990.
103. Galizzi J-P, Zuber CE, Harada N, Gorman DM, Djossou O, Kastelein R, Banchereau J, Howard M and Miyajima A: Molecular cloning of a cDNA encoding the human interleukin 4 receptor. Int Immunol 2: 669-675, 1990.
104. Dcichmann K, Bardutzky J, Forster J, Heinzmann A and Kuehr J: Common polymorphisms in the coding part of the IL4-receptor gene. Biochem Biophys Res Commun 231: 696-697, 1997.
105. Mitsuyasu H, Izuhara K, Mao X-Q, Gao P-S, Arinobu Y, Enomoto T, Kawai M, Sasaki S, Dakc Y, Hamasaki N, Shirakawa T and Hopkin JM: Ile50Val variant of IL4Rα upregulates IgE synthesis ans associates with atopic asthama. Nat Genet 19: 119-120, 1998.
106. Mitsuyasu H, Yanagihara Y, Mao X-Q, Gao P-S, Arinobu Y, Ihara K, Takabayashi A, Hara T, Enomoto T, Sasaki S, Kawai M, Hamasaki N, Shirakawa T, Hopkin JM and Izuhara K: Dominant effect of Ile50Val variant of the human intcrleukin-4 receptor ct chain in IgE synthesis. J Immunol (In press).
107. Imani F, Rager KJ, Catipovic B and Marsh DG: Interleukin-4 (IL-4) induces phosphatidylinositol 3-kinasc (p85) dephosphorylation. J Biol Chem 272: 7927-7931 1997