0 3 The the DT 4 8 AP-1 ap-1 NN 9 13 site site NN 14 16 at at IN 17 21 -150 -150 CD 22 24 bp bp NN 24 25 , , , 26 29 but but CC 30 33 not not RB 34 37 the the DT 38 46 NF-kappa NF-kappa NNP 47 48 B B NNP 49 53 site site NN 53 54 , , , 55 57 is be VBZ 58 64 likely likely JJ 65 67 to to TO 68 77 represent represent VB 78 81 the the DT 82 87 major major JJ 88 94 target target NN 95 97 of of IN 98 105 protein protein NN 106 112 kinase kinase NNP 113 114 C C NNP 115 117 in in IN 118 121 the the DT 122 133 interleukin interleukin NN 134 135 2 2 CD 136 144 promoter promoter NN 144 145 . . . 147 158 Stimulation stimulation NN 159 161 of of IN 162 163 T t NN 164 169 cells cell NNS 170 174 with with IN 175 182 antigen antigen NN 183 190 results result VBZ 191 193 in in IN 194 204 activation activation NN 205 207 of of IN 208 215 several several JJ 216 223 kinases kinase NNS 223 224 , , , 225 234 including include VBG 235 242 protein protein NN 243 249 kinase kinase NNP 250 251 C C NNP 252 253 ( ( ( 253 256 PKC PKC NNP 256 257 ) ) ) 257 258 , , , 259 263 that that WDT 264 267 may may MD 268 275 mediate mediate VB 276 279 the the DT 280 285 later later JJ 286 295 induction induction NN 296 298 of of IN 299 317 activation-related activation-related JJ 318 323 genes gene NNS 323 324 . . . 325 327 We we PRP 328 332 have have VBP 333 341 examined examine VBN 342 345 the the DT 346 355 potential potential JJ 356 360 role role NN 361 363 of of IN 364 367 PKC PKC NNP 368 370 in in IN 371 380 induction induction NN 381 383 of of IN 384 387 the the DT 388 399 interleukin interleukin NN 400 401 2 2 CD 402 403 ( ( ( 403 407 IL-2 il-2 NN 407 408 ) ) ) 409 413 gene gene NN 414 416 in in IN 417 418 T t NN 419 424 cells cell NNS 425 435 stimulated stimulate VBN 436 443 through through IN 444 447 the the DT 448 449 T t NN 450 454 cell cell NN 455 467 receptor/CD3 receptor/cd3 NN 468 475 complex complex NN 475 476 . . . 477 479 We we PRP 480 484 have have VBP 485 495 previously previously RB 496 501 shown show VBN 502 506 that that IN 507 516 prolonged prolonged JJ 517 526 treatment treatment NN 527 529 of of IN 530 533 the the DT 534 547 untransformed untransformed JJ 548 549 T t NN 550 554 cell cell NN 555 560 clone clone NN 561 565 Ar-5 ar-5 NN 566 570 with with IN 571 578 phorbol phorbol NN 579 585 esters ester NNS 586 593 results result VBZ 594 596 in in IN 597 611 downmodulation downmodulation NN 612 614 of of IN 615 618 the the DT 619 624 alpha alpha NN 625 628 and and CC 629 633 beta beta NN 634 642 isozymes isozyme NNS 643 645 of of IN 646 649 PKC PKC NNP 649 650 , , , 651 654 and and CC 655 664 abrogates abrogate VBZ 665 674 induction induction NN 675 677 of of IN 678 682 IL-2 il-2 NN 683 687 mRNA mRNA NNP 688 691 and and CC 692 699 protein protein NN 699 700 . . . 701 705 Here here RB 706 708 we we PRP 709 713 show show VBP 714 718 that that IN 719 726 phorbol phorbol NN 727 732 ester ester NN 733 742 treatment treatment NN 743 747 also also RB 748 757 abolishes abolish VBZ 758 767 induction induction NN 768 770 of of IN 771 786 chloramphenicol chloramphenicol NN 787 804 acetyltransferase acetyltransferase NN 805 813 activity activity NN 814 816 in in IN 817 821 Ar-5 ar-5 NN 822 827 cells cell NNS 828 839 transfected transfecte VBN 840 844 with with IN 845 846 a a DT 847 854 plasmid plasmid NN 855 865 containing contain VBG 866 869 the the DT 870 874 IL-2 il-2 NN 875 883 promoter promoter NN 884 890 linked link VBN 891 893 to to TO 894 898 this this DT 899 907 reporter reporter NN 908 912 gene gene NN 912 913 . . . 914 917 The the DT 918 922 IL-2 il-2 NN 923 931 promoter promoter NN 932 940 contains contain VBZ 941 948 binding bind VBG 949 954 sites site NNS 955 958 for for IN 959 966 nuclear nuclear JJ 967 974 factors factor NNS 975 984 including include VBG 985 991 NFAT-1 nfat-1 NN 991 992 , , , 993 996 Oct Oct NNP 996 997 , , , 998 1006 NF-kappa NF-kappa NNP 1007 1008 B B NNP 1008 1009 , , , 1010 1013 and and CC 1014 1018 AP-1 ap-1 NN 1018 1019 , , , 1020 1025 which which WDT 1026 1029 are be VBP 1030 1033 all all RB 1034 1045 potentially potentially RB 1046 1055 sensitive sensitive JJ 1056 1058 to to TO 1059 1069 activation activation NN 1070 1072 of of IN 1073 1076 PKC PKC NNP 1076 1077 . . . 1078 1080 We we PRP 1081 1085 show show VBP 1086 1090 that that IN 1091 1100 induction induction NN 1101 1103 of of IN 1104 1105 a a DT 1106 1112 trimer trimer NN 1113 1115 of of IN 1116 1119 the the DT 1120 1124 NFAT NFAT NNP 1125 1128 and and CC 1129 1132 Oct Oct NNP 1133 1138 sites site NNS 1139 1141 is be VBZ 1142 1145 not not RB 1146 1155 sensitive sensitive JJ 1156 1158 to to TO 1159 1166 phorbol phorbol NN 1167 1172 ester ester NN 1173 1182 treatment treatment NN 1182 1183 , , , 1184 1187 and and CC 1188 1192 that that IN 1193 1202 mutations mutation NNS 1203 1205 in in IN 1206 1209 the the DT 1210 1218 NF-kappa NF-kappa NNP 1219 1220 B B NNP 1221 1225 site site NN 1226 1230 have have VBP 1231 1233 no no DT 1234 1240 effect effect NN 1241 1243 on on IN 1244 1256 inducibility inducibility NN 1257 1259 of of IN 1260 1263 the the DT 1264 1268 IL-2 il-2 NN 1269 1277 promoter promoter NN 1277 1278 . . . 1279 1281 In in IN 1282 1290 contrast contrast NN 1290 1291 , , , 1292 1301 mutations mutation NNS 1302 1304 in in IN 1305 1308 the the DT 1309 1313 AP-1 ap-1 NN 1314 1318 site site NN 1319 1326 located located JJ 1327 1329 at at IN 1330 1334 -150 -150 CD 1335 1337 bp bp NN 1338 1344 almost almost RB 1345 1355 completely completely RB 1356 1364 abrogate abrogate VBP 1365 1374 induction induction NN 1375 1377 of of IN 1378 1381 the the DT 1382 1386 IL-2 il-2 NN 1387 1395 promoter promoter NN 1395 1396 , , , 1397 1400 and and CC 1401 1411 appearance appearance NN 1412 1414 of of IN 1415 1417 an an DT 1418 1427 inducible inducible JJ 1428 1435 nuclear nuclear JJ 1436 1442 factor factor NN 1443 1450 binding bind VBG 1451 1453 to to TO 1454 1458 this this DT 1459 1463 site site NN 1464 1466 is be VBZ 1467 1476 sensitive sensitive JJ 1477 1479 to to TO 1480 1483 PKC PKC NNP 1484 1493 depletion depletion NN 1493 1494 . . . 1495 1503 Moreover moreover RB 1503 1504 , , , 1505 1520 cotransfections cotransfection NNS 1521 1525 with with IN 1526 1531 c-fos c-fos NN 1532 1535 and and CC 1536 1541 c-jun c-jun NN 1542 1552 expression expression NN 1553 1561 plasmids plasmid NNS 1562 1570 markedly markedly RB 1571 1578 enhance enhance VBP 1579 1588 induction induction NN 1589 1591 of of IN 1592 1595 the the DT 1596 1600 IL-2 il-2 NN 1601 1609 promoter promoter NN 1610 1612 in in IN 1613 1622 minimally minimally RB 1623 1633 stimulated stimulate VBN 1634 1635 T t NN 1636 1641 cells cell NNS 1641 1642 . . . 1643 1646 Our our PRP$ 1647 1654 results result NNS 1655 1663 indicate indicate VBP 1664 1668 that that IN 1669 1672 the the DT 1673 1677 AP-1 ap-1 NN 1678 1682 site site NN 1683 1685 at at IN 1686 1690 -150 -150 CD 1691 1693 bp bp NN 1694 1704 represents represent VBZ 1705 1706 a a DT 1707 1712 major major JJ 1712 1713 , , , 1714 1716 if if IN 1717 1720 not not RB 1721 1724 the the DT 1725 1729 only only JJ 1729 1730 , , , 1731 1735 site site NN 1736 1738 of of IN 1739 1742 PKC PKC NNP 1743 1757 responsiveness responsiveness NN 1758 1760 in in IN 1761 1764 the the DT 1765 1769 IL-2 il-2 NN 1770 1778 promoter promoter NN 1778 1779 . . .