0 8 NF-kappa NF-kappa NNP 9 10 B B NNP 11 21 activation activation NN 22 24 by by IN 25 30 tumor tumor NN 31 39 necrosis necrosis NN 40 46 factor factor NN 47 52 alpha alpha NN 53 55 in in IN 56 59 the the DT 60 66 Jurkat Jurkat NNP 67 68 T t NN 69 73 cell cell NN 74 78 line line NN 79 81 is be VBZ 82 93 independent independent JJ 94 96 of of IN 97 104 protein protein NN 105 111 kinase kinase NNP 112 113 A A NNP 113 114 , , , 115 122 protein protein NN 123 129 kinase kinase NNP 130 131 C C NNP 131 132 , , , 133 136 and and CC 137 153 Ca(2+)-regulated ca(2+)-regulated JJ 154 161 kinases kinase NNS 161 162 . . . 164 172 NF-kappa NF-kappa NNP 173 174 B B NNP 175 177 is be VBZ 178 179 a a DT 180 191 DNA-binding dna-binding JJ 192 202 regulatory regulatory JJ 203 209 factor factor NN 210 214 able able JJ 215 217 to to TO 218 225 control control VB 226 239 transcription transcription NN 240 242 of of IN 243 244 a a DT 245 251 number number NN 252 254 of of IN 255 260 genes gene NNS 260 261 , , , 262 271 including include VBG 272 277 human human JJ 278 294 immunodeficiency immunodeficiency NN 295 300 virus virus NN 301 302 ( ( ( 302 305 HIV HIV NNP 305 306 ) ) ) 307 312 genes gene NNS 312 313 . . . 314 316 In in IN 317 318 T t NN 319 324 cells cell NNS 324 325 , , , 326 334 NF-kappa NF-kappa NNP 335 336 B B NNP 337 339 is be VBZ 340 349 activated activate VBN 350 354 upon upon IN 355 363 cellular cellular JJ 364 373 treatment treatment NN 374 376 by by IN 377 384 phorbol phorbol NN 385 391 esters ester NNS 392 395 and and CC 396 399 the the DT 400 408 cytokine cytokine NN 409 414 tumor tumor NN 415 423 necrosis necrosis NN 424 430 factor factor NN 431 436 alpha alpha NN 437 438 ( ( ( 438 441 TNF TNF NNP 442 447 alpha alpha NN 447 448 ) ) ) 448 449 . . . 450 452 In in IN 453 456 the the DT 457 464 present present JJ 465 469 work work NN 469 470 , , , 471 473 we we PRP 474 486 investigated investigate VBD 487 490 the the DT 491 500 molecular molecular JJ 501 507 events event NNS 508 515 leading lead VBG 516 518 to to TO 519 527 NF-kappa NF-kappa NNP 528 529 B B NNP 530 540 activation activation NN 541 543 by by IN 544 547 TNF TNF NNP 548 553 alpha alpha NN 554 556 in in IN 557 558 a a DT 559 564 human human JJ 565 566 T t NN 567 571 cell cell NN 572 576 line line NN 577 578 ( ( ( 578 584 Jurkat Jurkat NNP 584 585 ) ) ) 586 589 and and CC 590 593 its its PRP$ 594 602 subclone subclone NN 603 607 JCT6 jct6 NN 607 608 , , , 609 614 which which WDT 615 623 presents present VBZ 624 625 a a DT 626 636 deficiency deficiency NN 637 639 in in IN 640 643 the the DT 644 647 PKA PKA NNP 648 660 transduction transduction NN 661 668 pathway pathway NN 668 669 . . . 670 672 We we PRP 673 678 found find VBD 679 683 that that IN 684 686 in in IN 687 691 both both DT 692 696 cell cell NN 697 702 lines line NNS 702 703 , , , 704 708 both both CC 709 716 phorbol phorbol NN 717 722 ester ester NN 723 726 and and CC 727 730 TNF tnf NN 731 736 alpha alpha NN 737 741 were be VBD 742 746 able able JJ 747 749 to to TO 750 758 activate activate VB 759 767 NF-kappa NF-kappa NNP 768 770 B. B. NNP 771 778 Phorbol Phorbol NNP 779 789 activation activation NN 790 793 was be VBD 794 804 positively positively RB 805 814 modulated modulate VBN 815 817 by by IN 818 822 Ca2+ ca2+ NN 823 829 influx influx NN 830 835 while while IN 836 839 TNF TNF NNP 840 845 alpha alpha NN 846 856 activation activation NN 857 860 was be VBD 861 864 not not RB 864 865 . . . 866 877 Furthermore furthermore RB 877 878 , , , 879 884 while while IN 885 888 PMA PMA NNP 889 899 activation activation NN 900 903 was be VBD 904 913 inhibited inhibit VBN 914 916 by by IN 917 920 the the DT 921 924 PKC PKC NNP 925 934 inhibitor inhibitor NN 935 947 staurosporin staurosporin NN 947 948 , , , 949 952 the the DT 953 956 TNF TNF NNP 957 962 alpha alpha NN 963 969 effect effect NN 970 973 was be VBD 974 983 unchanged unchanged JJ 983 984 . . . 985 988 TNF TNF NNP 989 994 alpha alpha NN 995 998 did do VBD 999 1002 not not RB 1003 1011 activate activate VB 1012 1016 cAMP camp NN 1017 1027 production production NN 1028 1031 and and CC 1032 1035 its its PRP$ 1036 1042 signal signal NN 1043 1046 was be VBD 1047 1050 not not RB 1051 1060 modulated modulate VBN 1061 1063 by by IN 1064 1068 cAMP camp NN 1069 1079 activators activator NNS 1079 1080 . . . 1081 1089 Moreover moreover RB 1089 1090 , , , 1091 1095 cAMP camp NN 1096 1106 activators activator NNS 1107 1110 did do VBD 1111 1114 not not RB 1115 1123 activate activate VB 1124 1132 NF-kappa NF-kappa NNP 1133 1134 B B NNP 1135 1137 in in IN 1138 1144 Jurkat Jurkat NNP 1145 1150 cells cell NNS 1150 1151 . . . 1152 1156 Thus thus RB 1156 1157 , , , 1158 1161 TNF TNF NNP 1162 1175 alpha-induced alpha-induced JJ 1176 1184 NF-kappa NF-kappa NNP 1185 1186 B B NNP 1187 1197 activation activation NN 1198 1201 was be VBD 1202 1207 found find VBN 1208 1210 to to TO 1211 1213 be be VB 1214 1222 mediated mediate VBN 1223 1225 by by IN 1226 1230 none none NN 1231 1233 of of IN 1234 1237 the the DT 1238 1243 major major JJ 1244 1260 signal-mediating signal-mediating JJ 1261 1268 kinases kinase NNS 1269 1273 such such JJ 1274 1276 as as IN 1277 1284 protein protein NN 1285 1291 kinase kinase NNP 1292 1293 C C NNP 1294 1295 ( ( ( 1295 1298 PKC PKC NNP 1298 1299 ) ) ) 1299 1300 , , , 1301 1308 protein protein NN 1309 1315 kinase kinase NNP 1316 1317 A A NNP 1317 1318 , , , 1319 1321 or or CC 1322 1338 Ca(2+)-regulated ca(2+)-regulated JJ 1339 1346 kinases kinase NNS 1346 1347 . . . 1348 1359 Furthermore furthermore RB 1359 1360 , , , 1361 1363 we we PRP 1364 1369 found find VBD 1370 1374 that that IN 1375 1386 cytoplasmic cytoplasmic JJ 1387 1400 acidification acidification NN 1401 1412 facilitated facilitate VBD 1413 1421 NF-kappa NF-kappa NNP 1422 1423 B B NNP 1424 1434 activation activation NN 1435 1437 by by IN 1438 1442 both both CC 1443 1446 TNF TNF NNP 1447 1452 alpha alpha NN 1453 1456 and and CC 1457 1460 PKC PKC NNP 1460 1461 , , , 1462 1464 by by IN 1465 1466 a a DT 1467 1476 mechanism mechanism NN 1477 1481 that that WDT 1482 1491 increases increase VBZ 1492 1500 NF-kappa NF-kappa NNP 1501 1504 B/I B/I NNP 1505 1510 kappa kappa NN 1511 1512 B B NNP 1513 1525 dissociation dissociation NN 1526 1533 without without IN 1534 1543 affecting affect VBG 1544 1547 the the DT 1548 1556 NF-kappa NF-kappa NNP 1557 1558 B B NNP 1559 1572 translocation translocation NN 1573 1577 step step NN 1577 1578 . . .