0 10 Uncoupling uncouple VBG 11 31 activation-dependent activation-dependent JJ 32 35 HS1 hs1 NN 36 51 phosphorylation phosphorylation NN 52 56 from from IN 57 64 nuclear nuclear JJ 65 71 factor factor NN 72 74 of of IN 75 84 activated activate VBN 85 86 T t NN 87 92 cells cell NNS 93 108 transcriptional transcriptional JJ 109 119 activation activation NN 120 122 in in IN 123 129 Jurkat Jurkat NNP 130 131 T t NN 132 137 cells cell NNS 137 138 : : : 139 151 differential differential JJ 152 161 signaling signaling NN 162 169 through through IN 170 173 CD3 CD3 NNP 174 177 and and CC 178 181 the the DT 182 195 costimulatory costimulatory JJ 196 205 receptors receptor NNS 206 209 CD2 cd2 NN 210 213 and and CC 214 218 CD28 cd28 NN 218 219 . . . 221 224 CD3 CD3 NNP 224 225 , , , 226 229 CD2 CD2 NNP 229 230 , , , 231 234 and and CC 235 239 CD28 cd28 NN 240 243 are be VBP 244 256 functionally functionally RB 257 265 distinct distinct JJ 266 275 receptors receptor NNS 276 278 on on IN 279 280 T t NN 281 292 lymphocytes lymphocyte NNS 292 293 . . . 294 304 Engagement engagement NN 305 307 of of IN 308 311 any any DT 312 314 of of IN 315 320 these these DT 321 330 receptors receptor NNS 331 338 induces induce VBZ 339 342 the the DT 343 348 rapid rapid JJ 349 357 tyrosine tyrosine NN 358 373 phosphorylation phosphorylation NN 374 376 of of IN 377 378 a a DT 379 385 shared shared JJ 386 391 group group NN 392 394 of of IN 395 408 intracellular intracellular JJ 409 418 signaling signaling NN 419 427 proteins protein NNS 427 428 , , , 429 438 including include VBG 439 442 Vav Vav NNP 442 443 , , , 444 447 Cbl Cbl NNP 447 448 , , , 449 452 p85 p85 NN 453 469 phosphoinositide phosphoinositide NN 470 478 3-kinase 3-kinase NNP 478 479 , , , 480 483 and and CC 484 487 the the DT 488 491 Src Src NNP 492 498 family family NN 499 506 kinases kinase NNS 507 510 Lck Lck NNP 511 514 and and CC 515 518 Fyn Fyn NNP 518 519 . . . 520 528 Ligation Ligation NNP 529 531 of of IN 532 535 CD3 CD3 NNP 536 540 also also RB 541 548 induces induce VBZ 549 552 the the DT 553 561 tyrosine tyrosine NN 562 577 phosphorylation phosphorylation NN 578 580 of of IN 581 584 HS1 HS1 NNP 584 585 , , , 586 587 a a DT 588 594 75-kDa 75-kda JJ 595 608 hematopoietic hematopoietic JJ 609 622 cell-specific cell-specific JJ 623 636 intracellular intracellular JJ 637 646 signaling signaling NN 647 654 protein protein NN 655 657 of of IN 658 665 unknown unknown JJ 666 674 function function NN 674 675 . . . 676 678 We we PRP 679 683 have have VBP 684 692 examined examine VBN 693 700 changes change NNS 701 703 in in IN 704 707 HS1 hs1 NN 708 723 phosphorylation phosphorylation NN 724 729 after after IN 730 742 differential differential JJ 743 754 stimulation stimulation NN 755 757 of of IN 758 761 CD3 CD3 NNP 761 762 , , , 763 766 CD2 CD2 NNP 766 767 , , , 768 771 and and CC 772 776 CD28 cd28 NN 777 779 to to TO 780 789 elucidate elucidate VB 790 793 its its PRP$ 794 798 role role NN 799 801 in in IN 802 803 T t NN 804 809 cells cell NNS 810 813 and and CC 814 816 to to TO 817 824 further further RB 825 834 delineate delineate VB 835 838 the the DT 839 848 signaling signaling NN 849 857 pathways pathway NNS 858 867 recruited recruit VBN 868 870 by by IN 871 876 these these DT 877 886 receptors receptor NNS 886 887 . . . 888 894 Unlike unlike IN 895 903 ligation ligation NN 904 906 of of IN 907 910 CD3 CD3 NNP 910 911 , , , 912 923 stimulation stimulation NN 924 928 with with IN 929 938 anti-CD28 anti-cd28 JJ 939 942 mAb mab NN 943 945 or or CC 946 949 CHO cho NN 950 955 cells cell NNS 956 966 expressing express VBG 967 970 the the DT 971 975 CD28 cd28 NN 976 983 ligands ligand NNS 984 988 CD80 CD80 NNP 989 991 or or CC 992 996 CD86 CD86 NNP 997 1000 did do VBD 1001 1004 not not RB 1005 1009 lead lead VB 1010 1012 to to TO 1013 1021 tyrosine tyrosine NN 1022 1037 phosphorylation phosphorylation NN 1038 1040 of of IN 1041 1044 HS1 hs1 NN 1045 1047 in in IN 1048 1054 Jurkat Jurkat NNP 1055 1056 T t NN 1057 1062 cells cell NNS 1062 1063 . . . 1064 1076 Additionally additionally RB 1076 1077 , , , 1078 1080 no no DT 1081 1089 tyrosine tyrosine NN 1090 1105 phosphorylation phosphorylation NN 1106 1108 of of IN 1109 1112 HS1 HS1 NNP 1113 1116 was be VBD 1117 1124 induced induce VBN 1125 1127 by by IN 1128 1137 mitogenic mitogenic JJ 1138 1143 pairs pair NNS 1144 1146 of of IN 1147 1155 anti-CD2 anti-cd2 JJ 1156 1160 mAbs mab NNS 1161 1168 capable capable JJ 1169 1171 of of IN 1172 1182 activating activate VBG 1183 1186 the the DT 1187 1200 transcription transcription NN 1201 1207 factor factor NN 1208 1212 NFAT NFAT NNP 1213 1214 ( ( ( 1214 1221 nuclear nuclear JJ 1222 1228 factor factor NN 1229 1231 of of IN 1232 1241 activated activate VBN 1242 1243 T t NN 1244 1249 cells cell NNS 1249 1250 ) ) ) 1250 1251 . . . 1252 1265 Costimulation costimulation NN 1266 1273 through through IN 1274 1278 CD28 cd28 NN 1279 1285 and/or and/or CC 1286 1289 CD2 cd2 NN 1290 1293 did do VBD 1294 1297 not not RB 1298 1306 modulate modulate VB 1307 1310 the the DT 1311 1324 CD3-dependent cd3-dependent JJ 1325 1340 phosphorylation phosphorylation NN 1341 1343 of of IN 1344 1347 HS1 HS1 NNP 1347 1348 . . . 1349 1351 In in FW 1352 1356 vivo vivo FW 1357 1364 studies study NNS 1365 1374 indicated indicate VBD 1375 1379 that that IN 1380 1391 CD3-induced cd3-induced JJ 1392 1395 HSI HSI NNP 1396 1411 phosphorylation phosphorylation NN 1412 1415 was be VBD 1416 1425 dependent dependent JJ 1426 1430 upon upon IN 1431 1435 both both CC 1436 1439 the the DT 1440 1443 Src src NN 1444 1450 family family NN 1451 1459 tyrosine tyrosine NN 1460 1466 kinase kinase NNP 1467 1470 Lck Lck NNP 1471 1474 and and CC 1475 1478 the the DT 1479 1487 tyrosine tyrosine NN 1488 1499 phosphatase phosphatase NN 1500 1504 CD45 CD45 NNP 1504 1505 , , , 1506 1509 did do VBD 1510 1513 not not RB 1514 1521 require require VB 1522 1526 MEK1 mek1 NN 1527 1533 kinase kinase NNP 1534 1542 activity activity NN 1542 1543 , , , 1544 1547 and and CC 1548 1551 was be VBD 1552 1561 regulated regulate VBN 1562 1564 by by IN 1565 1572 protein protein NN 1573 1579 kinase kinase NNP 1580 1581 C C NNP 1582 1592 activation activation NN 1592 1593 . . . 1594 1598 Thus thus RB 1598 1599 , , , 1600 1608 although although IN 1609 1612 CD3 CD3 NNP 1612 1613 , , , 1614 1618 CD28 cd28 NN 1618 1619 , , , 1620 1623 and and CC 1624 1627 CD2 cd2 NN 1628 1636 activate activate VBP 1637 1641 many many JJ 1642 1644 of of IN 1645 1648 the the DT 1649 1653 same same JJ 1654 1663 signaling signal VBG 1664 1673 molecules molecule NNS 1673 1674 , , , 1675 1679 they they PRP 1680 1688 differed differ VBD 1689 1691 in in IN 1692 1697 their their PRP$ 1698 1706 capacity capacity NN 1707 1709 to to TO 1710 1716 induce induce VB 1717 1720 the the DT 1721 1729 tyrosine tyrosine NN 1730 1745 phosphorylation phosphorylation NN 1746 1748 of of IN 1749 1752 HSI HSI NNP 1752 1753 . . . 1754 1765 Furthermore furthermore RB 1765 1766 , , , 1767 1787 activation-dependent activation-dependent JJ 1788 1796 tyrosine tyrosine NN 1797 1812 phosphorylation phosphorylation NN 1813 1815 of of IN 1816 1819 HS1 HS1 NNP 1820 1823 was be VBD 1824 1827 not not RB 1828 1836 required require VBN 1837 1840 for for IN 1841 1845 NFAT NFAT NNP 1846 1861 transcriptional transcriptional JJ 1862 1872 activation activation NN 1872 1873 . . .