0 10 Inhibition Inhibition NNP 11 13 of of IN 14 21 protein protein NN 22 34 phosphatases phosphatas NNS 35 37 by by IN 38 45 okadaic okadaic JJ 46 50 acid acid NN 51 58 induces induce VBZ 59 62 AP1 ap1 NN 63 65 in in IN 66 71 human human JJ 72 73 T t NN 74 79 cells cell NNS 79 80 . . . 82 84 To to TO 85 92 examine examine VB 93 96 the the DT 97 101 role role NN 102 104 of of IN 105 112 protein protein NN 113 125 phosphatases phosphatas NNS 126 128 in in IN 129 130 T t NN 131 135 cell cell NN 136 146 activation activation NN 146 147 , , , 148 154 Jurkat Jurkat NNP 155 160 cells cell NNS 161 165 were be VBD 166 173 treated treat VBN 174 178 with with IN 179 186 okadaic okadaic JJ 187 191 acid acid NN 191 192 , , , 193 195 an an DT 196 205 inhibitor inhibitor NN 206 208 of of IN 209 213 type type NN 214 215 1 1 CD 216 219 and and CC 220 222 2A 2a NN 223 235 phosphatases phosphatas NNS 235 236 , , , 237 240 and and CC 241 248 nuclear nuclear JJ 249 257 extracts extract NNS 258 262 were be VBD 263 271 examined examine VBN 272 275 for for IN 276 279 the the DT 280 288 presence presence NN 289 291 of of IN 292 295 AP1 ap1 NN 296 298 as as IN 299 300 a a DT 301 308 measure measure NN 309 311 of of IN 312 317 early early JJ 318 319 T t NN 320 324 cell cell NN 325 335 activation activation NN 335 336 . . . 337 344 Okadaic okadaic JJ 345 349 acid acid NN 350 353 was be VBD 354 359 found find VBN 360 362 to to TO 363 365 be be VB 366 367 a a DT 368 374 potent potent JJ 375 382 inducer inducer NN 383 385 of of IN 386 389 AP1 AP1 NNP 389 390 . . . 391 393 In in IN 394 402 contrast contrast NN 403 405 to to TO 406 413 phorbol phorbol NN 414 420 esters ester NNS 421 425 such such JJ 426 428 as as IN 429 436 phorbol phorbol NN 437 446 myristate myristate NN 447 454 acetate acetate NN 455 456 ( ( ( 456 459 PMA PMA NNP 459 460 ) ) ) 460 461 , , , 462 465 the the DT 466 475 induction induction NN 476 478 of of IN 479 482 AP1 ap1 NN 483 485 by by IN 486 493 okadaic okadaic JJ 494 498 acid acid NN 499 505 occurs occur VBZ 506 519 predominantly predominantly RB 520 522 by by IN 523 538 transcriptional transcriptional JJ 539 549 activation activation NN 550 552 of of IN 553 556 the the DT 557 560 jun jun NN 561 564 and and CC 565 568 fos fos NN 569 575 family family NN 576 578 of of IN 579 594 proto-oncogenes proto-oncogene NNS 594 595 . . . 596 608 Surprisingly surprisingly RB 608 609 , , , 610 615 while while IN 616 619 the the DT 620 628 addition addition NN 629 631 of of IN 632 650 phytohemagglutinin phytohemagglutinin NN 651 658 further further RBR 659 667 enhanced enhance VBD 668 671 the the DT 672 681 induction induction NN 682 684 of of IN 685 688 AP1 AP1 NNP 688 689 , , , 690 693 the the DT 694 702 addition addition NN 703 705 of of IN 706 709 PMA PMA NNP 710 719 inhibited inhibit VBD 720 722 it it PRP 722 723 . . . 724 731 Okadaic okadaic JJ 732 736 acid acid NN 737 746 treatment treatment NN 747 750 was be VBD 751 756 found find VBN 757 759 to to TO 760 772 dramatically dramatically RB 773 781 increase increase VB 782 786 mRNA mrna NN 787 798 transcripts transcript NNS 799 801 of of IN 802 805 the the DT 806 809 jun jun NN 810 816 family family NN 817 819 of of IN 820 835 proto-oncogenes proto-oncogene NNS 836 845 including include VBG 846 851 c-jun c-jun NN 851 852 , , , 853 857 junD jund NN 857 858 , , , 859 862 and and CC 863 867 junB junB NNP 868 871 and and CC 872 874 to to TO 875 876 a a DT 877 883 lesser less JJR 884 890 extent extent NN 891 894 the the DT 895 898 fos fos NN 899 905 family family NN 906 915 including include VBG 916 921 c-fos c-fos NN 922 925 and and CC 926 931 fra-1 fra-1 NN 931 932 . . . 933 935 By by IN 936 946 comparison comparison NN 946 947 , , , 948 951 PMA PMA NNP 952 954 is be VBZ 955 956 a a DT 957 961 very very RB 962 973 inefficient inefficient JJ 974 981 inducer inducer NN 982 984 of of IN 985 988 the the DT 989 992 jun jun NN 993 997 gene gene NN 998 1004 family family NN 1005 1007 in in IN 1008 1014 Jurkat Jurkat NNP 1015 1020 cells cell NNS 1020 1021 . . . 1022 1029 Similar similar JJ 1030 1032 to to TO 1033 1036 its its PRP$ 1037 1043 effect effect NN 1044 1046 on on IN 1047 1050 the the DT 1051 1060 induction induction NN 1061 1063 of of IN 1064 1067 AP1 ap1 NN 1068 1070 by by IN 1071 1078 okadaic okadaic JJ 1079 1083 acid acid NN 1083 1084 , , , 1085 1088 PMA PMA NNP 1089 1097 inhibits inhibit VBZ 1098 1101 the the DT 1102 1111 induction induction NN 1112 1114 of of IN 1115 1120 c-jun c-jun NN 1121 1125 mRNA mrna NN 1126 1128 by by IN 1129 1136 okadaic okadaic JJ 1137 1141 acid acid NN 1141 1142 . . . 1143 1155 Transfection transfection NN 1156 1158 of of IN 1159 1164 c-jun c-jun NN 1165 1173 promoter promoter NN 1174 1184 constructs construct NNS 1185 1194 confirmed confirm VBD 1195 1198 the the DT 1199 1205 marked marked JJ 1206 1216 difference difference NN 1217 1224 between between IN 1225 1228 PMA PMA NNP 1229 1232 and and CC 1233 1240 okadaic okadaic JJ 1241 1245 acid acid NN 1246 1248 in in IN 1249 1257 inducing induce VBG 1258 1263 c-jun c-jun NN 1264 1277 transcription transcription NN 1277 1278 . . . 1279 1282 The the DT 1283 1292 induction induction NN 1293 1295 of of IN 1296 1299 AP1 ap1 NN 1300 1302 by by IN 1303 1310 okadaic okadaic JJ 1311 1315 acid acid NN 1316 1324 suggests suggest VBZ 1325 1329 that that IN 1330 1337 protein protein NN 1338 1350 phosphatases phosphatas NNS 1351 1352 1 1 CD 1353 1356 and and CC 1357 1359 2A 2a NN 1360 1361 ( ( ( 1361 1364 PP1 PP1 NNP 1365 1368 and and CC 1369 1373 PP2A PP2A NNP 1373 1374 ) ) ) 1375 1378 may may MD 1379 1381 be be VB 1382 1390 involved involve VBN 1391 1393 in in IN 1394 1395 T t NN 1396 1400 cell cell NN 1401 1411 activation activation NN 1412 1414 as as IN 1415 1424 important important JJ 1425 1433 negative negative JJ 1434 1444 regulators regulator NNS 1445 1447 of of IN 1448 1451 the the DT 1452 1465 transcription transcription NN 1466 1472 factor factor NN 1473 1476 AP1 ap1 NN 1476 1477 . . .