0 7 Signals signal NNS 8 11 and and CC 12 19 nuclear nuclear JJ 20 27 factors factor NNS 28 32 that that WDT 33 41 regulate regulate VBP 42 45 the the DT 46 56 expression expression NN 57 59 of of IN 60 73 interleukin-4 interleukin-4 NN 74 77 and and CC 78 91 interleukin-5 interleukin-5 NN 92 97 genes gene NNS 98 100 in in IN 101 107 helper helper NN 108 109 T t NN 110 115 cells cell NNS 115 116 . . . 118 123 Mouse Mouse NNP 124 131 thymoma thymoma NN 132 136 line line NN 137 141 EL-4 el-4 NN 142 147 cells cell NNS 148 155 produce produce VBP 156 165 cytokines cytokine NNS 166 170 such such JJ 171 173 as as IN 174 185 interleukin interleukin NN 186 187 ( ( ( 187 192 IL)-2 IL)-2 NNP 192 193 , , , 194 198 IL-3 IL-3 NNP 198 199 , , , 200 204 IL-4 il-4 NN 204 205 , , , 206 211 IL-10 IL-10 NNP 211 212 , , , 213 216 and and CC 217 239 granulocyte-macrophage granulocyte-macrophage JJ 240 258 colony-stimulating colony-stimulating JJ 259 265 factor factor NN 266 268 in in IN 269 277 response response NN 278 280 to to TO 281 288 phorbol phorbol NN 289 301 12-myristate 12-myristate NN 302 312 13-acetate 13-acetate NN 313 314 ( ( ( 314 317 PMA PMA NNP 317 318 ) ) ) 318 319 . . . 320 324 EL-4 el-4 NN 325 330 cells cell NNS 331 335 also also RB 336 343 produce produce VBP 344 347 low low JJ 348 354 levels level NNS 355 357 of of IN 358 362 IL-5 il-5 NN 363 367 when when WRB 368 378 stimulated stimulate VBN 379 381 by by IN 382 385 PMA PMA NNP 386 391 alone alone RB 391 392 ; ; : 393 400 however however RB 400 401 , , , 402 406 cAMP cAMP NNP 407 414 greatly greatly RB 415 423 augments augment VBZ 424 437 PMA-dependent pma-dependent JJ 438 442 IL-5 IL-5 NNP 443 453 production production NN 453 454 . . . 455 456 A a DT 457 466 transient transient JJ 467 479 transfection transfection NN 480 485 assay assay NN 486 494 revealed reveal VBD 495 499 that that IN 500 503 two two CD 504 511 signals signal NNS 511 512 , , , 513 516 PMA PMA NNP 517 520 and and CC 521 525 cAMP cAMP NNP 525 526 , , , 527 530 are be VBP 531 539 required require VBN 540 543 for for IN 544 551 optimal optimal JJ 552 562 activation activation NN 563 565 of of IN 566 569 the the DT 570 574 IL-5 il-5 NN 575 583 promoter promoter NN 583 584 . . . 585 587 In in IN 588 596 contrast contrast NN 596 597 , , , 598 602 cAMP camp NN 603 609 almost almost RB 610 620 completely completely RB 621 630 inhibited inhibit VBD 631 634 the the DT 635 648 PMA-dependent pma-dependent JJ 649 659 activation activation NN 660 662 of of IN 663 666 the the DT 667 677 endogenous endogenous JJ 678 682 IL-2 il-2 NN 683 687 gene gene NN 687 688 , , , 689 691 as as RB 692 696 well well RB 697 699 as as IN 700 703 the the DT 704 715 transfected transfecte VBN 716 720 IL-2 il-2 NN 721 729 promoter promoter NN 729 730 . . . 731 736 These these DT 737 744 results result NNS 745 753 indicate indicate VBP 754 758 that that IN 759 762 the the DT 763 767 IL-5 IL-5 NNP 768 772 gene gene NN 773 775 is be VBZ 776 786 positively positively RB 787 796 regulated regulate VBN 797 799 by by IN 800 804 cAMP camp NN 805 807 in in IN 808 809 a a DT 810 816 manner manner NN 817 825 opposite opposite JJ 826 828 to to TO 829 833 that that DT 834 837 for for IN 838 841 the the DT 842 846 IL-2 il-2 NN 847 851 gene gene NN 851 852 . . . 853 856 One one CD 857 859 of of IN 860 863 the the DT 864 871 nuclear nuclear JJ 872 879 factors factor NNS 880 881 ( ( ( 881 884 NFs NF NNP 884 885 ) ) ) 886 890 that that WDT 891 900 regulates regulate VBZ 901 904 the the DT 905 913 response response NN 914 916 of of IN 917 920 the the DT 921 925 IL-5 IL-5 NNP 926 934 promoter promoter NN 935 937 to to TO 938 942 cAMP cAMP NNP 943 946 and and CC 947 950 PMA PMA NNP 951 954 has have VBZ 955 965 properties property NNS 966 973 similar similar JJ 974 976 to to TO 977 979 NF NF NNP 980 983 for for IN 984 993 activated activate VBN 994 995 t t NN 996 1000 cell cell NN 1000 1001 . . . 1002 1005 The the DT 1006 1007 P p NN 1008 1016 sequence sequence NN 1017 1019 of of IN 1020 1023 the the DT 1024 1028 IL-4 il-4 NN 1029 1033 gene gene NN 1033 1034 , , , 1035 1042 defined define VBN 1043 1045 as as IN 1046 1047 a a DT 1048 1058 responsive responsive JJ 1059 1066 element element NN 1067 1070 for for IN 1071 1074 PMA PMA NNP 1075 1078 and and CC 1079 1086 calcium calcium NN 1087 1096 ionophore ionophore NN 1097 1098 ( ( ( 1098 1104 A23187 A23187 NNP 1104 1105 ) ) ) 1105 1106 , , , 1107 1113 shares share VBZ 1114 1122 sequence sequence NN 1123 1133 similarity similarity NN 1134 1138 with with IN 1139 1142 the the DT 1143 1145 NF NF NNP 1146 1151 kappa kappa NN 1152 1153 B B NNP 1154 1157 and and CC 1158 1161 the the DT 1162 1174 NF-activated nf-activated JJ 1175 1176 T t NN 1177 1181 cell cell NN 1182 1189 binding binding NN 1190 1195 sites site NNS 1195 1196 . . . 1197 1199 We we PRP 1200 1209 attempted attempt VBD 1210 1212 to to TO 1213 1222 determine determine VB 1223 1230 whether whether IN 1231 1236 NF(P) NF(P) NNP 1236 1237 , , , 1238 1239 a a DT 1240 1247 nuclear nuclear JJ 1248 1254 factor factor NN 1255 1263 specific specific JJ 1264 1267 for for IN 1268 1271 the the DT 1272 1273 P p NN 1274 1282 sequence sequence NN 1282 1283 , , , 1284 1286 is be VBZ 1287 1294 related related JJ 1295 1297 to to TO 1298 1306 NF-kappa NF-kappa NNP 1307 1308 B B NNP 1309 1312 and and CC 1313 1320 nuclear nuclear JJ 1321 1327 factor factor NN 1328 1331 for for IN 1332 1341 activated activate VBN 1342 1343 T t NN 1344 1348 cell cell NN 1349 1350 ( ( ( 1350 1355 NF-AT NF-AT NNP 1355 1356 ) ) ) 1356 1357 . . . 1358 1360 In in IN 1361 1376 electromobility electromobility NN 1377 1382 shift shift NN 1383 1389 assays assay NNS 1390 1394 both both CC 1395 1403 NF-kappa NF-kappa NNP 1404 1405 B B NNP 1406 1407 ( ( ( 1407 1410 P65 P65 NNP 1411 1413 or or CC 1414 1421 P65/P50 P65/P50 NNP 1422 1433 heterodimer heterodimer NN 1433 1434 ) ) ) 1435 1438 and and CC 1439 1444 NF-AT NF-AT NNP 1445 1450 bound bind VBD 1451 1453 to to TO 1454 1457 the the DT 1458 1459 P p NN 1460 1468 sequence sequence NN 1468 1469 . . . 1470 1477 However however RB 1477 1478 , , , 1479 1487 sequence sequence NN 1488 1499 specificity specificity NN 1500 1502 of of IN 1503 1508 NF-AT NF-AT NNP 1509 1512 was be VBD 1513 1517 more more RBR 1518 1525 similar similar JJ 1526 1528 to to TO 1529 1533 that that DT 1534 1536 of of IN 1537 1542 NF(P) nf(p) NN 1542 1543 , , , 1544 1547 and and CC 1548 1552 only only RB 1553 1554 a a DT 1555 1560 small small JJ 1561 1567 amount amount NN 1568 1570 of of IN 1571 1574 P65 P65 NNP 1575 1578 was be VBD 1579 1587 detected detect VBN 1588 1590 in in IN 1591 1596 NF(P) NF(P) NNP 1596 1597 . . . 1598 1603 These these DT 1604 1611 results result NNS 1612 1620 indicate indicate VBP 1621 1625 that that IN 1626 1627 a a DT 1628 1637 component component NN 1638 1640 or or CC 1641 1651 components component NNS 1652 1654 of of IN 1655 1660 NF-AT NF-AT NNP 1661 1665 have have VBP 1666 1669 the the DT 1670 1679 potential potential NN 1680 1682 to to TO 1683 1695 reconstitute reconstitute VB 1696 1701 NF(P) nf(p) NN 1701 1702 , , , 1703 1710 whereas whereas IN 1711 1719 NF-kappa NF-kappa NNP 1720 1721 B B NNP 1722 1727 alone alone RB 1728 1732 does do VBZ 1733 1736 not not RB 1737 1744 account account VB 1745 1748 for for IN 1749 1754 NF(P) NF(P) NNP 1755 1757 in in IN 1758 1764 Jurkat Jurkat NNP 1765 1770 crude crude JJ 1771 1778 extract extract NN 1778 1779 . . . 1780 1785 Taken take VBN 1786 1794 together together RB 1794 1795 , , , 1796 1801 these these DT 1802 1809 results result NNS 1810 1817 suggest suggest VBP 1818 1822 that that IN 1823 1833 NF-AT-like nf-at-like JJ 1834 1841 factors factor NNS 1842 1845 are be VBP 1846 1854 involved involve VBN 1855 1857 in in IN 1858 1861 the the DT 1862 1872 regulation regulation NN 1873 1875 of of IN 1876 1880 IL-4 il-4 NN 1881 1884 and and CC 1885 1889 IL-5 il-5 NN 1890 1895 genes gene NNS 1895 1896 . . .