0 4 MEK1 MEK1 NNP 5 8 and and CC 9 12 the the DT 13 26 extracellular extracellular JJ 27 43 signal-regulated signal-regulated JJ 44 51 kinases kinase NNS 52 55 are be VBP 56 64 required require VBN 65 68 for for IN 69 72 the the DT 73 84 stimulation stimulation NN 85 87 of of IN 88 92 IL-2 il-2 NN 93 97 gene gene NN 98 111 transcription transcription NN 112 114 in in IN 115 116 T t NN 117 122 cells cell NNS 122 123 . . . 125 128 TCR TCR NNP 129 139 engagement engagement NN 140 150 stimulates stimulate VBZ 151 154 the the DT 155 165 activation activation NN 166 168 of of IN 169 172 the the DT 173 180 protein protein NN 181 187 kinase kinase NNP 188 193 Raf-1 Raf-1 NNP 193 194 . . . 195 201 Active active JJ 202 207 Raf-1 raf-1 NN 208 222 phosphorylates phosphorylate VBZ 223 226 and and CC 227 236 activates activate VBZ 237 240 the the DT 241 258 mitogen-activated mitogen-activated JJ 259 266 protein protein NN 267 268 ( ( ( 268 271 MAP MAP NNP 271 272 ) ) ) 273 293 kinase/extracellular kinase/extracellular JJ 294 310 signal-regulated signal-regulated JJ 311 317 kinase kinase NNP 318 324 kinase kinase NNP 325 326 1 1 CD 327 328 ( ( ( 328 332 MEK1 MEK1 NNP 332 333 ) ) ) 333 334 , , , 335 340 which which WDT 341 343 in in IN 344 348 turn turn NN 349 363 phosphorylates phosphorylate VBZ 364 367 and and CC 368 377 activates activate VBZ 378 381 the the DT 382 385 MAP MAP NNP 386 407 kinases/extracellular kinases/extracellular JJ 408 414 signal signal NN 415 424 regulated regulated JJ 425 432 kinases kinase NNS 432 433 , , , 434 438 ERK1 ERK1 NNP 439 442 and and CC 443 447 ERK2 ERK2 NNP 447 448 . . . 449 454 Raf-1 raf-1 NN 455 463 activity activity NN 464 472 promotes promote VBZ 473 477 IL-2 il-2 NN 478 488 production production NN 489 491 in in IN 492 501 activated activate VBN 502 503 T t NN 504 515 lymphocytes lymphocyte NNS 515 516 . . . 517 526 Therefore therefore RB 526 527 , , , 528 530 we we PRP 531 537 sought seek VBD 538 540 to to TO 541 550 determine determine VB 551 558 whether whether IN 559 563 MEK1 MEK1 NNP 564 567 and and CC 568 571 ERK ERK NNP 572 582 activities activity NNS 583 587 also also RB 588 597 stimulate stimulate VBP 598 602 IL-2 il-2 NN 603 607 gene gene NN 608 621 transcription transcription NN 621 622 . . . 623 633 Expression expression NN 634 636 of of IN 637 651 constitutively constitutively RB 652 658 active active JJ 659 664 Raf-1 raf-1 NN 665 667 or or CC 668 672 MEK1 mek1 NN 673 675 in in IN 676 682 Jurkat Jurkat NNP 683 684 T t NN 685 690 cells cell NNS 691 699 enhanced enhance VBD 700 703 the the DT 704 715 stimulation stimulation NN 716 718 of of IN 719 723 IL-2 il-2 NN 724 739 promoter-driven promoter-driven JJ 740 753 transcription transcription NN 754 764 stimulated stimulate VBN 765 767 by by IN 768 769 a a DT 770 777 calcium calcium NN 778 787 ionophore ionophore NN 788 791 and and CC 792 795 PMA PMA NNP 795 796 , , , 797 800 and and CC 801 809 together together RB 810 814 with with IN 815 816 a a DT 817 824 calcium calcium NN 825 834 ionophore ionophore NN 835 838 the the DT 839 849 expression expression NN 850 852 of of IN 853 857 each each DT 858 865 protein protein NN 866 869 was be VBD 870 880 sufficient sufficient JJ 881 883 to to TO 884 893 stimulate stimulate VB 894 899 NF-AT nf-at NN 900 908 activity activity NN 908 909 . . . 910 920 Expression expression NN 921 923 of of IN 924 940 MEK1-interfering mek1-interfering NN 941 948 mutants mutant NNS 949 958 inhibited inhibit VBD 959 962 the the DT 963 974 stimulation stimulation NN 975 977 of of IN 978 982 IL-2 il-2 NN 983 998 promoter-driven promoter-driven JJ 999 1012 transcription transcription NN 1013 1016 and and CC 1017 1024 blocked block VBD 1025 1028 the the DT 1029 1036 ability ability NN 1037 1039 of of IN 1040 1054 constitutively constitutively RB 1055 1061 active active JJ 1062 1065 Ras ras NN 1066 1069 and and CC 1070 1075 Raf-1 raf-1 NN 1076 1078 to to TO 1079 1090 costimulate costimulate VB 1091 1096 NF-AT nf-at NN 1097 1105 activity activity NN 1106 1110 with with IN 1111 1112 a a DT 1113 1120 calcium calcium NN 1121 1130 ionophore ionophore NN 1130 1131 . . . 1132 1142 Expression expression NN 1143 1145 of of IN 1146 1149 the the DT 1150 1153 MAP MAP NNP 1154 1169 kinase-specific kinase-specific JJ 1170 1181 phosphatase phosphatase NN 1181 1182 , , , 1183 1188 MKP-1 mkp-1 NN 1188 1189 , , , 1190 1195 which which WDT 1196 1202 blocks block VBZ 1203 1206 ERK erk NN 1207 1217 activation activation NN 1217 1218 , , , 1219 1228 inhibited inhibit VBD 1229 1233 IL-2 il-2 NN 1234 1242 promoter promoter NN 1243 1246 and and CC 1247 1259 NF-AT-driven nf-at-driven JJ 1260 1273 transcription transcription NN 1274 1284 stimulated stimulate VBN 1285 1287 by by IN 1288 1289 a a DT 1290 1297 calcium calcium NN 1298 1307 ionophore ionophore NN 1308 1311 and and CC 1312 1315 PMA PMA NNP 1315 1316 , , , 1317 1320 and and CC 1321 1323 in in IN 1324 1332 addition addition NN 1332 1333 , , , 1334 1339 MKP-1 mkp-1 NN 1340 1351 neutralized neutralize VBD 1352 1355 the the DT 1356 1371 transcriptional transcriptional JJ 1372 1383 enhancement enhancement NN 1384 1390 caused cause VBN 1391 1393 by by IN 1394 1400 active active JJ 1401 1406 Raf-1 raf-1 NN 1407 1410 and and CC 1411 1415 MEK1 mek1 NN 1416 1426 expression expression NN 1426 1427 . . . 1428 1430 We we PRP 1431 1439 conclude conclude VBP 1440 1444 that that IN 1445 1448 the the DT 1449 1452 MAP MAP NNP 1453 1459 kinase kinase NNP 1460 1466 signal signal NN 1467 1479 transduction transduction NN 1480 1487 pathway pathway NN 1488 1498 consisting consist VBG 1499 1501 of of IN 1502 1507 Raf-1 Raf-1 NNP 1507 1508 , , , 1509 1513 MEK1 MEK1 NNP 1513 1514 , , , 1515 1518 and and CC 1519 1523 ERK1 erk1 NN 1524 1527 and and CC 1528 1532 ERK2 erk2 NN 1533 1542 functions function NNS 1543 1545 in in IN 1546 1549 the the DT 1550 1561 stimulation stimulation NN 1562 1566 IL-2 il-2 NN 1567 1571 gene gene NN 1572 1585 transcription transcription NN 1586 1588 in in IN 1589 1598 activated activate VBN 1599 1600 T t NN 1601 1612 lymphocytes lymphocyte NNS 1612 1613 . . .