0 9 Long-term long-term JJ 10 18 inositol inositol NN 19 28 phosphate phosphate NN 29 36 release release NN 36 37 , , , 38 41 but but CC 42 45 not not RB 46 54 tyrosine tyrosine NN 55 61 kinase kinase NNP 62 70 activity activity NN 70 71 , , , 72 82 correlates correlate VBZ 83 87 with with IN 88 92 IL-2 il-2 NN 93 102 secretion secretion NN 103 106 and and CC 107 112 NF-AT nf-at NN 113 122 induction induction NN 123 125 in in IN 126 144 anti-CD3-activated anti-cd3-activated JJ 145 155 peripheral peripheral JJ 156 161 human human JJ 162 163 T t NN 164 175 lymphocytes lymphocyte NNS 175 176 . . . 178 181 The the DT 182 189 cascade cascade NN 190 192 of of IN 193 199 events event NNS 200 206 within within IN 207 210 the the DT 211 216 first first JJ 217 220 few few JJ 221 228 minutes minute NNS 229 231 of of IN 232 233 T t NN 234 238 cell cell NN 239 250 stimulation stimulation NN 251 254 has have VBZ 255 259 been be VBN 260 264 well well RB 265 278 characterized characterize VBN 278 279 . . . 280 288 Although although IN 289 293 many many JJ 294 300 second second JJ 301 311 messengers messenger NNS 312 316 have have VBP 317 321 been be VBN 322 327 shown show VBN 328 330 to to TO 331 333 be be VB 334 343 necessary necessary JJ 344 347 and and CC 348 358 sufficient sufficient JJ 359 362 for for IN 363 364 T t NN 365 369 cell cell NN 370 380 activation activation NN 381 383 in in IN 384 385 a a DT 386 392 number number NN 393 395 of of IN 396 401 model model NN 402 409 systems system NNS 409 410 , , , 411 414 the the DT 415 428 rate-limiting rate-limiting JJ 429 433 step step NN 434 436 in in IN 437 447 peripheral peripheral JJ 448 449 T t NN 450 455 cells cell NNS 456 459 has have VBZ 460 463 not not RB 464 468 been be VBN 469 481 demonstrated demonstrate VBN 481 482 . . . 483 485 To to TO 486 491 model model VB 492 501 effective effective JJ 502 508 versus versus IN 509 520 ineffective ineffective JJ 521 533 CD3-mediated cd3-mediated JJ 534 545 stimulation stimulation NN 546 548 in in IN 549 559 peripheral peripheral JJ 560 561 T t NN 562 567 cells cell NNS 567 568 , , , 569 571 we we PRP 572 576 used use VBD 577 580 two two CD 581 589 anti-CD3 anti-cd3 JJ 590 594 mAbs mab NNS 595 599 that that WDT 600 606 differ differ VBP 607 609 in in IN 610 615 their their PRP$ 616 623 ability ability NN 624 626 to to TO 627 636 stimulate stimulate VB 637 645 purified purify VBN 646 647 T t NN 648 653 cells cell NNS 653 654 : : : 655 659 OKT3 OKT3 NNP 659 660 , , , 661 666 which which WDT 667 673 causes cause VBZ 674 679 early early JJ 680 686 second second JJ 687 696 messenger messenger NN 697 707 generation generation NN 708 711 but but CC 712 714 is be VBZ 715 721 unable unable JJ 722 724 to to TO 725 733 activate activate VB 734 735 T t NN 736 741 cells cell NNS 742 749 without without IN 750 751 a a DT 752 758 second second JJ 759 765 signal signal NN 765 766 , , , 767 770 and and CC 771 775 64.1 64.1 CD 775 776 , , , 777 782 which which WDT 783 793 stimulates stimulate VBZ 794 795 T t NN 796 800 cell cell NN 801 814 proliferation proliferation NN 815 817 on on IN 818 821 its its PRP$ 822 825 own own JJ 825 826 . . . 827 829 We we PRP 830 835 found find VBD 836 840 that that IN 841 849 tyrosine tyrosine NN 850 856 kinase kinase NNP 857 865 activity activity NN 866 869 was be VBD 870 877 similar similar JJ 878 881 for for IN 882 886 both both DT 887 891 mAbs mab NNS 892 896 over over IN 897 898 a a DT 899 905 period period NN 906 908 of of IN 909 914 hours hour NNS 914 915 . . . 916 923 However however RB 923 924 , , , 925 928 the the DT 929 937 inositol inositol NN 938 947 phosphate phosphate NN 948 956 response response NN 957 960 was be VBD 961 969 stronger strong JJR 970 973 for for IN 974 978 64.1 64.1 CD 979 983 than than IN 984 987 for for IN 988 992 OKT3 OKT3 NNP 992 993 . . . 994 996 To to TO 997 1000 tie tie VB 1001 1006 these these DT 1007 1013 events event NNS 1014 1016 to to TO 1017 1021 gene gene NN 1022 1032 activation activation NN 1032 1033 , , , 1034 1036 we we PRP 1037 1045 measured measure VBD 1046 1054 NF-kappa NF-kappa NNP 1055 1056 B B NNP 1057 1060 and and CC 1061 1066 NF-AT NF-AT NNP 1067 1075 activity activity NN 1076 1078 in in IN 1079 1082 the the DT 1083 1090 nucleus nucleus NN 1091 1096 after after IN 1097 1105 anti-CD3 anti-cd3 JJ 1106 1117 stimulation stimulation NN 1117 1118 . . . 1119 1123 Both both DT 1124 1131 stimuli stimulus NNS 1132 1139 induced induce VBD 1140 1143 the the DT 1144 1154 appearance appearance NN 1155 1157 of of IN 1158 1161 the the DT 1162 1170 NF-kappa NF-kappa NNP 1171 1172 B B NNP 1173 1183 components component NNS 1184 1185 ( ( ( 1185 1190 c-Rel c-rel NN 1190 1191 , , , 1192 1195 p65 p65 NN 1196 1197 ( ( ( 1197 1201 RelA RelA NNP 1201 1202 ) ) ) 1202 1203 , , , 1204 1207 and and CC 1208 1211 p50 p50 NN 1212 1213 ( ( ( 1213 1221 NF-kappa NF-kappa NNP 1222 1224 B1 B1 NNP 1224 1225 ) ) ) 1225 1226 ) ) ) 1227 1230 and and CC 1231 1239 NF-kappa NF-kappa NNP 1240 1241 B B NNP 1242 1245 DNA DNA NNP 1246 1253 binding binding NN 1254 1262 activity activity NN 1263 1265 in in IN 1266 1269 the the DT 1270 1277 nucleus nucleus NN 1277 1278 . . . 1279 1286 However however RB 1286 1287 , , , 1288 1292 only only RB 1293 1297 64.1 64.1 CD 1298 1305 induced induce VBD 1306 1311 NF-AT nf-at NN 1312 1314 in in IN 1315 1318 the the DT 1319 1326 nucleus nucleus NN 1326 1327 , , , 1328 1339 correlating correlate VBG 1340 1344 with with IN 1345 1348 its its PRP$ 1349 1356 ability ability NN 1357 1359 to to TO 1360 1368 activate activate VB 1369 1370 T t NN 1371 1376 cells cell NNS 1376 1377 . . . 1378 1382 Thus thus RB 1382 1383 , , , 1384 1389 NF-AT NF-AT NNP 1390 1399 induction induction NN 1400 1403 and and CC 1404 1408 IL-2 il-2 NN 1409 1418 secretion secretion NN 1419 1423 were be VBD 1424 1434 correlated correlate VBN 1435 1439 with with IN 1440 1443 the the DT 1444 1450 levels level NNS 1451 1453 of of IN 1454 1462 inositol inositol NN 1463 1472 phosphate phosphate NN 1473 1480 release release NN 1481 1484 but but CC 1485 1488 not not RB 1489 1493 with with IN 1494 1499 gross gross JJ 1500 1506 levels level NNS 1507 1509 of of IN 1510 1518 tyrosine tyrosine NN 1519 1525 kinase kinase NNP 1526 1534 activity activity NN 1535 1542 induced induce VBN 1543 1547 late late RB 1548 1557 following follow VBG 1558 1561 the the DT 1562 1570 response response NN 1570 1571 . . . 1572 1574 On on IN 1575 1578 the the DT 1579 1584 other other JJ 1585 1589 hand hand NN 1589 1590 , , , 1591 1599 NF-kappa NF-kappa NNP 1600 1601 B B NNP 1602 1611 induction induction NN 1612 1615 and and CC 1616 1620 IL-2 il-2 NN 1621 1629 receptor receptor NN 1630 1640 expression expression NN 1641 1649 occurred occur VBD 1650 1654 even even RB 1655 1659 with with IN 1660 1663 the the DT 1664 1671 smaller small JJR 1672 1678 second second JJ 1679 1688 messenger messenger NN 1689 1697 response response NN 1698 1707 generated generate VBN 1708 1710 by by IN 1711 1715 OKT3 OKT3 NNP 1715 1716 . . .