0 11 Recombinant recombinant JJ 12 17 NFAT1 NFAT1 NNP 18 19 ( ( ( 19 24 NFATp NFATp NNP 24 25 ) ) ) 26 28 is be VBZ 29 38 regulated regulate VBN 39 41 by by IN 42 53 calcineurin calcineurin NN 54 56 in in IN 57 58 T t NN 59 64 cells cell NNS 65 68 and and CC 69 77 mediates mediate VBZ 78 91 transcription transcription NN 92 94 of of IN 95 102 several several JJ 103 111 cytokine cytokine NN 112 117 genes gene NNS 117 118 . . . 120 133 Transcription transcription NN 134 141 factors factor NNS 142 144 of of IN 145 148 the the DT 149 153 NFAT NFAT NNP 154 160 family family NN 161 165 play play VBP 166 167 a a DT 168 171 key key JJ 172 176 role role NN 177 179 in in IN 180 183 the the DT 184 197 transcription transcription NN 198 200 of of IN 201 209 cytokine cytokine NN 210 215 genes gene NNS 216 219 and and CC 220 225 other other JJ 226 231 genes gene NNS 232 238 during during IN 239 242 the the DT 243 249 immune immune JJ 250 258 response response NN 258 259 . . . 260 262 We we PRP 263 267 have have VBP 268 278 identified identify VBN 279 282 two two CD 283 286 new new JJ 287 295 isoforms isoform NNS 296 298 of of IN 299 302 the the DT 303 316 transcription transcription NN 317 323 factor factor NN 324 329 NFAT1 nfat1 NN 330 331 ( ( ( 331 341 previously previously RB 342 348 termed term VBN 349 354 NFATp NFATp NNP 354 355 ) ) ) 356 360 that that WDT 361 364 are be VBP 365 368 the the DT 369 380 predominant predominant JJ 381 389 isoforms isoform NNS 390 399 expressed express VBN 400 402 in in IN 403 409 murine murine JJ 410 413 and and CC 414 419 human human JJ 420 421 T t NN 422 427 cells cell NNS 427 428 . . . 429 433 When when WRB 434 443 expressed express VBN 444 446 in in IN 447 453 Jurkat Jurkat NNP 454 455 T t NN 456 461 cells cell NNS 461 462 , , , 463 474 recombinant recombinant JJ 475 480 NFAT1 nfat1 NN 481 483 is be VBZ 484 493 regulated regulate VBN 493 494 , , , 495 497 as as IN 498 506 expected expect VBN 506 507 , , , 508 510 by by IN 511 514 the the DT 515 535 calmodulin-dependent calmodulin-dependent JJ 536 547 phosphatase phosphatase NN 548 559 calcineurin calcineurin NN 559 560 , , , 561 564 and and CC 565 568 its its PRP$ 569 577 function function NN 578 580 is be VBZ 581 590 inhibited inhibit VBN 591 593 by by IN 594 597 the the DT 598 615 immunosuppressive immunosuppressive JJ 616 621 agent agent NN 622 633 cyclosporin cyclosporin NN 634 635 A A NNP 636 637 ( ( ( 637 640 CsA CsA NNP 640 641 ) ) ) 641 642 . . . 643 658 Transactivation Transactivation NNP 659 661 by by IN 662 673 recombinant recombinant JJ 674 679 NFAT1 nfat1 NN 680 682 in in IN 683 689 Jurkat Jurkat NNP 690 691 T t NN 692 697 cells cell NNS 698 706 requires require VBZ 707 711 dual dual JJ 712 723 stimulation stimulation NN 724 728 with with IN 729 738 ionomycin ionomycin NN 739 742 and and CC 743 750 phorbol phorbol NN 751 763 12-myristate 12-myristate NN 764 774 13-acetate 13-acetate NN 774 775 ; ; : 776 780 this this DT 781 789 activity activity NN 790 792 is be VBZ 793 804 potentiated potentiate VBN 805 807 by by IN 808 820 coexpression coexpression NN 821 823 of of IN 824 838 constitutively constitutively RB 839 845 active active JJ 846 857 calcineurin calcineurin NN 858 861 and and CC 862 864 is be VBZ 865 874 inhibited inhibit VBN 875 877 by by IN 878 881 CsA CsA NNP 881 882 . . . 883 901 Immunocytochemical immunocytochemical JJ 902 910 analysis analysis NN 911 920 indicates indicate VBZ 921 925 that that IN 926 937 recombinant recombinant JJ 938 943 NFAT1 nfat1 NN 944 953 localizes localize VBZ 954 956 in in IN 957 960 the the DT 961 970 cytoplasm cytoplasm NN 971 973 of of IN 974 985 transiently transiently RB 986 997 transfected transfecte VBN 998 999 T t NN 1000 1005 cells cell NNS 1006 1009 and and CC 1010 1022 translocates translocate VBZ 1023 1027 into into IN 1028 1031 the the DT 1032 1039 nucleus nucleus NN 1040 1042 in in IN 1043 1044 a a DT 1045 1058 CsA-sensitive csa-sensitive JJ 1059 1065 manner manner NN 1066 1075 following follow VBG 1076 1085 ionomycin ionomycin NN 1086 1097 stimulation stimulation NN 1097 1098 . . . 1099 1103 When when WRB 1104 1113 expressed express VBN 1114 1116 in in IN 1117 1120 COS COS NNP 1121 1126 cells cell NNS 1126 1127 , , , 1128 1135 however however RB 1135 1136 , , , 1137 1142 NFAT1 NFAT1 NNP 1143 1145 is be VBZ 1146 1153 capable capable JJ 1154 1156 of of IN 1157 1172 transactivation transactivation NN 1172 1173 , , , 1174 1177 but but CC 1178 1180 it it PRP 1181 1183 is be VBZ 1184 1187 not not RB 1188 1197 regulated regulate VBN 1198 1207 correctly correctly RB 1207 1208 : : : 1209 1212 its its PRP$ 1213 1224 subcellular subcellular JJ 1225 1237 localization localization NN 1238 1241 and and CC 1242 1257 transcriptional transcriptional JJ 1258 1266 function function NN 1267 1270 are be VBP 1271 1274 not not RB 1275 1283 affected affect VBN 1284 1286 by by IN 1287 1298 stimulation stimulation NN 1299 1301 of of IN 1302 1305 the the DT 1306 1309 COS COS NNP 1310 1315 cells cell NNS 1316 1320 with with IN 1321 1330 ionomycin ionomycin NN 1331 1334 and and CC 1335 1342 phorbol phorbol NN 1343 1355 12-myristate 12-myristate NN 1356 1366 13-acetate 13-acetate NN 1366 1367 . . . 1368 1379 Recombinant recombinant JJ 1380 1385 NFAT1 nfat1 NN 1386 1389 can can MD 1390 1397 mediate mediate VB 1398 1411 transcription transcription NN 1412 1414 of of IN 1415 1418 the the DT 1419 1432 interleukin-2 interleukin-2 NN 1432 1433 , , , 1434 1447 interleukin-4 interleukin-4 NN 1447 1448 , , , 1449 1454 tumor tumor NN 1455 1463 necrosis necrosis NN 1464 1470 factor factor NN 1471 1476 alpha alpha NN 1476 1477 , , , 1478 1481 and and CC 1482 1504 granulocyte-macrophage granulocyte-macrophage JJ 1505 1523 colony-stimulating colony-stimulating JJ 1524 1530 factor factor NN 1531 1540 promoters promoter NNS 1541 1543 in in IN 1544 1545 T t NN 1546 1551 cells cell NNS 1551 1552 , , , 1553 1563 suggesting suggest VBG 1564 1568 that that IN 1569 1574 NFAT1 nfat1 NN 1575 1586 contributes contribute VBZ 1587 1589 to to TO 1590 1593 the the DT 1594 1607 CsA-sensitive csa-sensitive JJ 1608 1621 transcription transcription NN 1622 1624 of of IN 1625 1630 these these DT 1631 1636 genes gene NNS 1637 1643 during during IN 1644 1647 the the DT 1648 1654 immune immune JJ 1655 1663 response response NN 1663 1664 . . .