0 10 Separation separation NN 11 13 of of IN 14 31 oxidant-initiated oxidant-initiated JJ 32 35 and and CC 36 51 redox-regulated redox-regulated JJ 52 57 steps step NNS 58 60 in in IN 61 64 the the DT 65 73 NF-kappa NF-kappa NNP 74 75 B B NNP 76 82 signal signal NN 83 95 transduction transduction NN 96 103 pathway pathway NN 103 104 . . . 106 113 Studies study NNS 114 123 presented present VBN 124 128 here here RB 129 133 show show VBP 134 138 that that IN 139 146 overall overall JJ 147 155 NF-kappa NF-kappa NNP 156 157 B B NNP 158 164 signal signal NN 165 177 transduction transduction NN 178 184 begins begin VBZ 185 189 with with IN 190 191 a a DT 192 200 parallel parallel JJ 201 207 series series NN 208 210 of of IN 211 227 stimuli-specific stimuli-specific JJ 228 236 pathways pathway NNS 237 244 through through IN 245 250 which which WDT 251 260 cytokines cytokine NNS 261 262 ( ( ( 262 267 tumor tumor NN 268 276 necrosis necrosis NN 277 283 factor factor NN 284 289 alpha alpha NN 289 290 ) ) ) 290 291 , , , 292 300 oxidants oxidant NNS 301 302 ( ( ( 302 310 hydrogen hydrogen NN 311 319 peroxide peroxide NN 320 323 and and CC 324 333 mitomycin mitomycin NN 334 335 C C NNP 335 336 ) ) ) 336 337 , , , 338 341 and and CC 342 349 phorbol phorbol NN 350 355 ester ester NN 356 357 ( ( ( 357 364 phorbol phorbol NN 365 377 12-myristate 12-myristate NN 378 388 13-acetate 13-acetate NN 388 389 ) ) ) 390 402 individually individually RB 403 411 initiate initiate VBP 412 421 signaling signaling NN 421 422 . . . 423 428 These these DT 429 436 initial initial JJ 437 445 pathways pathway NNS 446 455 culminate culminate VBP 456 458 in in IN 459 460 a a DT 461 467 common common JJ 468 475 pathway pathway NN 476 483 through through IN 484 489 which which WDT 490 493 all all DT 494 496 of of IN 497 500 the the DT 501 512 stimulating stimulate VBG 513 519 agents agent NNS 520 530 ultimately ultimately RB 531 537 signal signal VBP 538 546 NF-kappa NF-kappa NNP 547 548 B B NNP 549 559 activation activation NN 559 560 . . . 561 563 We we PRP 564 575 distinguish distinguish VBP 576 579 the the DT 580 596 stimuli-specific stimuli-specific JJ 597 605 pathways pathway NNS 606 608 by by IN 609 616 showing show VBG 617 621 that that IN 622 625 the the DT 626 635 oxidative oxidative JJ 636 643 stimuli stimulus NNS 644 651 trigger trigger VBP 652 660 NF-kappa NF-kappa NNP 661 662 B B NNP 663 673 activation activation NN 674 676 in in IN 677 681 only only RB 682 685 one one CD 686 688 of of IN 689 692 two two CD 693 698 human human JJ 699 705 T-cell t-cell NN 706 711 lines line NNS 712 713 ( ( ( 713 721 Wurzburg Wurzburg NNP 722 725 but but CC 726 729 not not RB 730 736 Jurkat Jurkat NNP 736 737 ) ) ) 737 738 , , , 739 746 whereas whereas IN 747 752 tumor tumor NN 753 761 necrosis necrosis NN 762 768 factor factor NN 769 774 alpha alpha NN 775 778 and and CC 779 786 phorbol phorbol NN 787 799 12-myristate 12-myristate NN 800 810 13-acetate 13-acetate NN 811 818 readily readily RB 819 828 stimulate stimulate VBP 829 831 in in IN 832 836 both both DT 837 842 lines line NNS 842 843 . . . 844 846 We we PRP 847 854 propose propose VBP 855 858 the the DT 859 865 common common JJ 866 873 pathway pathway NN 874 876 as as IN 877 880 the the DT 881 889 simplest simple JJS 890 893 way way NN 894 896 of of IN 897 907 accounting account VBG 908 911 for for IN 912 915 the the DT 916 922 common common JJ 923 935 requirements requirement NNS 936 939 and and CC 940 950 properties property NNS 951 953 of of IN 954 957 the the DT 958 967 signaling signaling NN 968 975 pathway pathway NN 975 976 . . . 977 979 We we PRP 980 987 include include VBP 988 989 a a DT 990 1006 redox-regulatory redox-regulatory JJ 1007 1019 mechanism(s) mechanism(s) NN 1020 1022 in in IN 1023 1027 this this DT 1028 1034 common common JJ 1035 1042 pathway pathway NN 1043 1045 to to TO 1046 1053 account account VB 1054 1057 for for IN 1058 1061 the the DT 1062 1072 previously previously RB 1073 1085 demonstrated demonstrate VBN 1086 1091 redox redox NN 1092 1102 regulation regulation NN 1103 1105 of of IN 1106 1114 NF-kappa NF-kappa NNP 1115 1116 B B NNP 1117 1127 activation activation NN 1128 1130 in in IN 1131 1137 Jurkat Jurkat NNP 1138 1143 cells cell NNS 1144 1145 ( ( ( 1145 1147 in in IN 1148 1153 which which WDT 1154 1162 oxidants oxidant NNS 1163 1165 do do VBP 1165 1168 n’t n't RB 1169 1177 activate activate VB 1178 1186 NF-kappa NF-kappa NNP 1187 1188 B B NNP 1188 1189 ) ) ) 1189 1190 ; ; : 1191 1193 we we PRP 1194 1197 put put VBP 1198 1206 tyrosine tyrosine NN 1207 1222 phosphorylation phosphorylation NN 1223 1225 in in IN 1226 1229 the the DT 1230 1236 common common JJ 1237 1244 pathway pathway NN 1245 1247 by by IN 1248 1255 showing show VBG 1256 1260 that that IN 1261 1267 kinase kinase NNP 1268 1276 activity activity NN 1277 1278 ( ( ( 1278 1289 inhibitable inhibitable JJ 1290 1292 by by IN 1293 1303 herbimycin herbimycin NN 1304 1305 A a NN 1306 1309 and and CC 1310 1320 tyrphostin tyrphostin NN 1321 1323 47 47 CD 1323 1324 ) ) ) 1325 1327 is be VBZ 1328 1336 required require VBN 1337 1340 for for IN 1341 1349 NF-kappa NF-kappa NNP 1350 1351 B B NNP 1352 1362 activation activation NN 1363 1365 by by IN 1366 1369 all all DT 1370 1377 stimuli stimulus NNS 1378 1384 tested test VBN 1385 1387 in in IN 1388 1392 both both DT 1393 1397 cell cell NN 1398 1403 lines line NNS 1403 1404 . . . 1405 1410 Since since IN 1411 1419 internal internal JJ 1420 1425 sites site NNS 1426 1428 of of IN 1429 1436 oxidant oxidant JJ 1437 1447 production production NN 1448 1452 have have VBP 1453 1457 been be VBN 1458 1463 shown show VBN 1464 1466 to to TO 1467 1471 play play VB 1472 1473 a a DT 1474 1477 key key JJ 1478 1482 role role NN 1483 1485 in in IN 1486 1489 the the DT 1490 1509 cytokine-stimulated cytokine-stimulated JJ 1510 1520 activation activation NN 1521 1523 of of IN 1524 1532 NF-kappa NF-kappa NNP 1533 1534 B B NNP 1534 1535 , , , 1536 1539 and and CC 1540 1545 since since IN 1546 1554 tyrosine tyrosine NN 1555 1561 kinase kinase NNP 1562 1565 and and CC 1566 1577 phosphatase phosphatase NN 1578 1588 activities activity NNS 1589 1592 are be VBP 1593 1598 known know VBN 1599 1601 to to TO 1602 1604 be be VB 1605 1612 altered alter VBN 1613 1615 by by IN 1616 1624 oxidants oxidant NNS 1624 1625 , , , 1626 1631 these these DT 1632 1640 findings finding NNS 1641 1648 suggest suggest VBP 1649 1653 that that IN 1654 1667 intracellular intracellular JJ 1668 1673 redox redox NN 1674 1680 status status NN 1681 1689 controls control VBZ 1690 1698 NF-kappa NF-kappa NNP 1699 1700 B B NNP 1701 1711 activation activation NN 1712 1714 by by IN 1715 1725 regulating regulate VBG 1726 1734 tyrosine tyrosine NN 1735 1750 phosphorylation phosphorylation NN 1751 1759 event(s) event(s) NN 1760 1766 within within IN 1767 1770 the the DT 1771 1777 common common JJ 1778 1782 step step NN 1783 1785 of of IN 1786 1789 the the DT 1790 1798 NF-kappa NF-kappa NNP 1799 1800 B B NNP 1801 1807 signal signal NN 1808 1820 transduction transduction NN 1821 1828 pathway pathway NN 1828 1829 . . .