0 11 Interleukin Interleukin NNP 12 13 4 4 CD 14 23 activates activate VBZ 24 25 a a DT 26 32 signal signal NN 33 43 transducer transducer NN 44 47 and and CC 48 57 activator activator NN 58 60 of of IN 61 74 transcription transcription NN 75 76 ( ( ( 76 80 Stat Stat NNP 80 81 ) ) ) 82 89 protein protein NN 90 95 which which WDT 96 105 interacts interact VBZ 106 110 with with IN 111 113 an an DT 114 130 interferon-gamma interferon-gamma NN 131 141 activation activation NN 142 151 site-like site-like JJ 152 160 sequence sequence NN 161 169 upstream upstream JJ 170 172 of of IN 173 176 the the DT 177 178 I i NN 179 186 epsilon epsilon NN 187 191 exon exon NN 192 194 in in IN 195 196 a a DT 197 202 human human JJ 203 204 B B NNP 205 209 cell cell NN 210 214 line line NN 214 215 . . . 216 224 Evidence evidence NN 225 228 for for IN 229 232 the the DT 233 244 involvement involvement NN 245 247 of of IN 248 253 Janus Janus NNP 254 260 kinase kinase NNP 261 262 3 3 CD 263 266 and and CC 267 280 interleukin-4 interleukin-4 NN 281 286 Stat. Stat. NNP 288 292 Germ Germ NNP 293 297 line line NN 298 299 C C NNP 300 311 transcripts transcript NNS 312 315 can can MD 316 318 be be VB 319 326 induced induce VBN 327 329 by by IN 330 334 IL-4 il-4 NN 335 337 in in IN 338 341 the the DT 342 347 human human JJ 348 349 B B NNP 350 354 cell cell NN 355 359 line line NN 359 360 , , , 361 365 BL-2 bl-2 NN 365 366 . . . 367 376 Utilizing utilize VBG 377 378 a a DT 379 388 IFN-gamma IFN-gamma NNP 389 399 activation activation NN 400 409 site-like site-like JJ 410 413 DNA dna NN 414 422 sequence sequence NN 423 430 element element NN 431 438 located located JJ 439 447 upstream upstream RB 448 450 of of IN 451 454 the the DT 455 456 I i NN 457 464 epsilon epsilon NN 465 469 exon exon NN 469 470 , , , 471 473 we we PRP 474 486 demonstrated demonstrate VBD 487 489 by by IN 490 493 gel gel NN 494 502 mobility mobility NN 503 508 shift shift NN 509 515 assays assay NNS 516 520 that that IN 521 525 IL-4 il-4 NN 526 533 induced induce VBD 534 535 a a DT 536 543 binding binding NN 544 552 activity activity NN 553 555 in in IN 556 559 the the DT 560 567 cytosol cytosol NN 568 571 and and CC 572 579 nucleus nucleus NN 580 582 of of IN 583 587 BL-2 bl-2 NN 588 593 cells cell NNS 593 594 . . . 595 599 This this DT 600 606 factor factor NN 607 610 was be VBD 611 621 designated designate VBN 622 626 IL-4 il-4 NN 627 630 NAF NAF NNP 631 632 ( ( ( 632 644 IL-4-induced il-4-induced JJ 645 663 nuclear-activating nuclear-activating JJ 664 671 factors factor NNS 671 672 ) ) ) 673 676 and and CC 677 680 was be VBD 681 691 identified identify VBN 692 694 as as IN 695 696 a a DT 697 705 tyrosine tyrosine NN 706 720 phosphoprotein phosphoprotein NN 720 721 , , , 722 727 which which WDT 728 740 translocates translocate VBZ 741 745 from from IN 746 749 the the DT 750 757 cytosol cytosol NN 758 760 to to TO 761 764 the the DT 765 772 nucleus nucleus NN 773 777 upon upon IN 778 782 IL-4 il-4 NN 783 792 treatment treatment NN 792 793 . . . 794 801 Because because IN 802 807 these these DT 808 811 are be VBP 812 815 the the DT 816 831 characteristics characteristic NNS 832 834 of of IN 835 836 a a DT 837 843 signal signal NN 844 854 transducer transducer NN 855 858 and and CC 859 868 activator activator NN 869 871 of of IN 872 885 transcription transcription NN 886 887 ( ( ( 887 891 Stat Stat NNP 891 892 ) ) ) 893 900 protein protein NN 900 901 , , , 902 904 we we PRP 905 915 determined determine VBD 916 923 whether whether IN 924 934 antibodies antibody NNS 935 937 to to TO 938 942 Stat Stat NNP 943 951 proteins protein NNS 952 956 will will MD 957 966 interfere interfere VB 967 971 with with IN 972 975 gel gel NN 976 984 mobility mobility NN 985 990 shift shift NN 991 994 and and CC 995 1000 found find VBD 1001 1005 that that IN 1006 1016 antibodies antibody NNS 1017 1019 to to TO 1020 1024 IL-4 il-4 NN 1025 1029 Stat Stat NNP 1029 1030 , , , 1031 1035 also also RB 1036 1041 known know VBN 1042 1044 as as IN 1045 1050 Stat6 Stat6 NNP 1050 1051 , , , 1052 1055 but but CC 1056 1059 not not RB 1060 1070 antibodies antibody NNS 1071 1073 to to TO 1074 1079 other other JJ 1080 1084 Stat Stat NNP 1085 1093 proteins protein NNS 1093 1094 , , , 1095 1104 interfere interfere VBP 1105 1109 with with IN 1110 1113 the the DT 1114 1123 formation formation NN 1124 1126 of of IN 1127 1130 the the DT 1131 1135 IL-4 il-4 NN 1136 1139 NAF naf NN 1140 1147 complex complex NN 1147 1148 . . . 1149 1158 Congruous congruous JJ 1159 1163 with with IN 1164 1167 the the DT 1168 1179 involvement involvement NN 1180 1182 of of IN 1183 1184 a a DT 1185 1189 Stat Stat NNP 1190 1197 protein protein NN 1197 1198 , , , 1199 1203 IL-4 il-4 NN 1204 1211 induced induce VBD 1212 1218 robust robust JJ 1219 1224 Janus Janus NNP 1225 1231 kinase kinase NNP 1232 1233 3 3 CD 1234 1235 ( ( ( 1235 1239 JAK3 jak3 NN 1239 1240 ) ) ) 1241 1249 activity activity NN 1250 1252 in in IN 1253 1257 BL-2 bl-2 NN 1258 1263 cells cell NNS 1263 1264 . . . 1265 1279 Cotransfection cotransfection NN 1280 1282 of of IN 1283 1287 JAK3 jak3 NN 1288 1292 with with IN 1293 1297 IL-4 il-4 NN 1298 1302 Stat Stat NNP 1303 1307 into into IN 1308 1313 COS-7 COS-7 NNP 1314 1319 cells cell NNS 1320 1328 produced produce VBD 1329 1331 an an DT 1332 1345 intracellular intracellular JJ 1346 1354 activity activity NN 1355 1360 which which WDT 1361 1366 bound bind VBD 1367 1370 the the DT 1371 1375 same same JJ 1376 1385 IFN-gamma IFN-gamma NNP 1386 1396 activation activation NN 1397 1406 site-like site-like JJ 1407 1415 sequence sequence NN 1416 1419 and and CC 1420 1430 comigrated comigrate VBD 1431 1435 with with IN 1436 1440 IL-4 il-4 NN 1441 1444 NAF naf NN 1445 1447 in in IN 1448 1463 electrophoretic electrophoretic JJ 1464 1472 mobility mobility NN 1473 1478 shift shift NN 1479 1484 assay assay NN 1484 1485 . . . 1486 1491 These these DT 1492 1499 results result NNS 1500 1504 show show VBP 1505 1509 that that IN 1510 1514 IL-4 il-4 NN 1515 1518 NAF NAF NNP 1519 1521 is be VBZ 1522 1526 IL-4 il-4 NN 1527 1531 Stat Stat NNP 1531 1532 , , , 1533 1538 which which WDT 1539 1541 is be VBZ 1542 1551 activated activate VBN 1552 1554 by by IN 1555 1559 JAK3 jak3 NN 1560 1562 in in IN 1563 1571 response response NN 1572 1574 to to TO 1575 1579 IL-4 il-4 NN 1580 1588 receptor receptor NN 1589 1599 engagement engagement NN 1599 1600 . . .