0 16 Homodimerization homodimerization NN 17 19 of of IN 20 23 the the DT 24 29 human human JJ 30 41 interleukin interleukin NN 42 43 4 4 CD 44 52 receptor receptor NN 53 58 alpha alpha NN 59 64 chain chain NN 65 72 induces induce VBZ 73 81 Cepsilon Cepsilon NNP 82 90 germline germline NN 91 102 transcripts transcript NNS 103 105 in in IN 106 107 B B NNP 108 113 cells cell NNS 114 116 in in IN 117 120 the the DT 121 128 absence absence NN 129 131 of of IN 132 135 the the DT 136 147 interleukin interleukin NN 148 149 2 2 CD 150 158 receptor receptor NN 159 164 gamma gamma NN 165 170 chain chain NN 170 171 . . . 173 176 The the DT 177 186 cytokines cytokine NNS 187 198 interleukin interleukin NN 199 200 ( ( ( 200 205 IL)-4 il)-4 NN 206 209 and and CC 210 215 IL-13 il-13 NN 216 220 play play VBP 221 222 a a DT 223 231 critical critical JJ 232 236 role role NN 237 239 in in IN 240 248 inducing induce VBG 249 257 Cepsilon Cepsilon NNP 258 266 germline germline NN 267 278 transcripts transcript NNS 279 282 and and CC 283 286 IgE ige NN 287 294 isotype isotype NN 295 304 switching switching NN 305 307 in in IN 308 313 human human JJ 314 315 B B NNP 316 321 cells cell NNS 321 322 . . . 323 326 The the DT 327 331 IL-4 il-4 NN 332 340 receptor receptor NN 341 342 ( ( ( 342 347 IL-4R IL-4R NNP 347 348 ) ) ) 349 351 in in IN 352 353 B B NNP 354 359 cells cell NNS 360 362 is be VBZ 363 371 composed compose VBN 372 374 of of IN 375 378 two two CD 379 385 chains chain NNS 385 386 , , , 387 390 the the DT 391 403 IL-4-binding il-4-binding JJ 404 414 IL-4Ralpha IL-4Ralpha NNP 415 420 chain chain NN 420 421 , , , 422 427 which which WDT 428 430 is be VBZ 431 437 shared share VBN 438 442 with with IN 443 446 the the DT 447 453 IL-13R il-13r NN 453 454 , , , 455 458 and and CC 459 462 the the DT 463 473 IL-2Rgamma IL-2Rgamma NNP 474 475 ( ( ( 475 481 gammac gammac NN 481 482 ) ) ) 483 488 chain chain NN 488 489 , , , 490 495 which which WDT 496 498 is be VBZ 499 505 shared share VBN 506 510 with with IN 511 516 IL-7R IL-7R NNP 516 517 , , , 518 523 IL-9R IL-9R NNP 523 524 , , , 525 528 and and CC 529 536 IL-15R. IL-15R. NNP 537 541 IL-4 il-4 NN 542 549 induces induce VBZ 550 558 Cepsilon Cepsilon NNP 559 567 germline germline NN 568 579 transcripts transcript NNS 580 583 and and CC 584 587 IgE ige NN 588 595 isotype isotype NN 596 605 switching switching NN 606 608 in in IN 609 610 B B NNP 611 616 cells cell NNS 617 621 from from IN 622 630 patients patient NNS 631 635 with with IN 636 642 gammac gammac NN 643 648 chain chain NN 649 659 deficiency deficiency NN 659 660 . . . 661 670 Induction Induction NNP 671 673 of of IN 674 682 Cepsilon Cepsilon NNP 683 691 germline germline NN 692 703 transcripts transcript NNS 704 706 by by IN 707 711 IL-4 il-4 NN 712 714 in in IN 715 716 B B NNP 717 722 cells cell NNS 723 727 that that WDT 728 732 lack lack VBP 733 736 the the DT 737 743 gammac gammac NN 744 749 chain chain NN 750 753 may may MD 754 761 involve involve VB 762 771 signaling signaling NN 772 775 via via IN 776 779 the the DT 780 787 IL-13R. IL-13R. NNP 788 801 Alternatively alternatively RB 801 802 , , , 803 806 the the DT 807 817 IL-4Ralpha IL-4Ralpha NNP 818 823 chain chain NN 824 827 may may MD 828 837 transduce transduce VB 838 851 intracellular intracellular JJ 852 859 signals signal NNS 860 864 that that WDT 865 869 lead lead VBP 870 872 to to TO 873 881 Cepsilon Cepsilon NNP 882 886 gene gene NN 887 900 transcription transcription NN 901 914 independently independently RB 915 917 of of IN 918 921 its its PRP$ 922 933 association association NN 934 938 with with IN 939 944 other other JJ 945 951 chains chain NNS 951 952 . . . 953 955 We we PRP 956 960 show show VBP 961 965 that that IN 966 980 ligand-induced ligand-induced JJ 981 997 homodimerization homodimerization NN 998 1000 of of IN 1001 1009 chimeric chimeric JJ 1010 1017 surface surface NN 1018 1027 receptors receptor NNS 1028 1038 consisting consist VBG 1039 1041 of of IN 1042 1045 the the DT 1046 1059 extracellular extracellular JJ 1060 1063 and and CC 1064 1077 transmembrane transmembrane JJ 1078 1085 domains domain NNS 1086 1088 of of IN 1089 1092 the the DT 1093 1107 erythropoietin erythropoietin NN 1108 1116 receptor receptor NN 1117 1120 and and CC 1121 1123 of of IN 1124 1127 the the DT 1128 1141 intracellular intracellular JJ 1142 1148 domain domain NN 1149 1151 of of IN 1152 1162 IL-4Ralpha IL-4Ralpha NNP 1163 1170 induces induce VBZ 1171 1176 Janus Janus NNP 1177 1183 kinase kinase NNP 1184 1185 1 1 CD 1186 1187 ( ( ( 1187 1191 Jak1 jak1 NN 1191 1192 ) ) ) 1193 1203 activation activation NN 1203 1204 , , , 1205 1210 STAT6 STAT6 NNP 1211 1221 activation activation NN 1221 1222 , , , 1223 1226 and and CC 1227 1235 Cepsilon Cepsilon NNP 1236 1244 germline germline NN 1245 1256 transcripts transcript NNS 1257 1259 in in IN 1260 1265 human human JJ 1266 1267 B B NNP 1268 1272 cell cell NN 1273 1277 line line NN 1278 1282 BJAB BJAB NNP 1282 1283 . . . 1284 1294 Disruption disruption NN 1295 1297 of of IN 1298 1301 the the DT 1302 1314 Jak1-binding jak1-binding JJ 1315 1327 proline-rich proline-rich JJ 1328 1332 Box1 box1 NN 1333 1339 region region NN 1340 1342 of of IN 1343 1353 IL-4Ralpha IL-4Ralpha NNP 1354 1363 abolished abolish VBD 1364 1373 signaling signaling NN 1374 1376 by by IN 1377 1381 this this DT 1382 1390 chimeric chimeric JJ 1391 1399 receptor receptor NN 1399 1400 . . . 1401 1412 Furthermore furthermore RB 1412 1413 , , , 1414 1415 B B NNP 1416 1421 cells cell NNS 1422 1433 transfected transfecte VBN 1434 1438 with with IN 1439 1440 a a DT 1441 1449 chimeric chimeric JJ 1450 1469 CD8alpha/IL-4Ralpha CD8alpha/IL-4Ralpha NNP 1470 1478 receptor receptor NN 1478 1479 , , , 1480 1485 which which WDT 1486 1488 is be VBZ 1489 1498 expressed express VBN 1499 1501 on on IN 1502 1505 the the DT 1506 1510 cell cell NN 1511 1518 surface surface NN 1519 1521 as as IN 1522 1523 a a DT 1524 1533 homodimer homodimer NN 1533 1534 , , , 1535 1549 constitutively constitutively RB 1550 1559 expressed express VBD 1560 1568 Cepsilon Cepsilon NNP 1569 1577 germline germline NN 1578 1589 transcripts transcript NNS 1589 1590 . . . 1591 1596 These these DT 1597 1604 results result NNS 1605 1612 suggest suggest VBP 1613 1617 that that IN 1618 1634 homodimerization homodimerization NN 1635 1637 of of IN 1638 1641 the the DT 1642 1652 IL-4Ralpha IL-4Ralpha NNP 1653 1658 chain chain NN 1659 1661 is be VBZ 1662 1672 sufficient sufficient JJ 1673 1675 to to TO 1676 1685 transduce transduce VB 1686 1700 Jak1-dependent jak1-dependent JJ 1701 1714 intracellular intracellular JJ 1715 1722 signals signal NNS 1723 1727 that that WDT 1728 1732 lead lead VBP 1733 1735 to to TO 1736 1739 IgE ige NN 1740 1747 isotype isotype NN 1748 1757 switching switching NN 1757 1758 . . .