0 6 SOCS-3 SOCS-3 NNP 7 9 is be VBZ 10 18 tyrosine tyrosine NN 19 33 phosphorylated phosphorylated JJ 34 36 in in IN 37 45 response response NN 46 48 to to TO 49 62 interleukin-2 interleukin-2 NN 63 66 and and CC 67 77 suppresses suppress VBZ 78 83 STAT5 stat5 NN 84 99 phosphorylation phosphorylation NN 100 103 and and CC 104 114 lymphocyte lymphocyte NN 115 128 proliferation proliferation NN 128 129 . . . 131 138 Members member NNS 139 141 of of IN 142 145 the the DT 146 154 recently recently RB 155 165 discovered discover VBN 166 178 SOCS/CIS/SSI SOCS/CIS/SSI NNP 179 185 family family NN 186 190 have have VBP 191 195 been be VBN 196 204 proposed propose VBN 205 207 as as IN 208 218 regulators regulator NNS 219 221 of of IN 222 230 cytokine cytokine NN 231 240 signaling signaling NN 240 241 , , , 242 245 and and CC 246 251 while while IN 252 259 targets target NNS 260 263 and and CC 264 274 mechanisms mechanism NNS 275 279 have have VBP 280 284 been be VBN 285 294 suggested suggest VBN 295 298 for for IN 299 303 some some DT 304 310 family family NN 311 318 members member NNS 318 319 , , , 320 323 the the DT 324 331 precise precise JJ 332 336 role role NN 337 339 of of IN 340 345 these these DT 346 354 proteins protein NNS 355 362 remains remain VBZ 363 365 to to TO 366 368 be be VB 369 376 defined define VBN 376 377 . . . 378 380 To to TO 381 385 date date VB 386 388 no no DT 389 393 SOCS SOCS NNP 394 402 proteins protein NNS 403 407 have have VBP 408 412 been be VBN 413 425 specifically specifically RB 426 436 implicated implicate VBN 437 439 in in IN 440 453 interleukin-2 interleukin-2 NN 454 455 ( ( ( 455 459 IL-2 il-2 NN 459 460 ) ) ) 461 470 signaling signaling NN 471 473 in in IN 474 475 T t NN 476 481 cells cell NNS 481 482 . . . 483 487 Here here RB 488 490 we we PRP 491 497 report report VBP 498 504 SOCS-3 socs-3 NN 505 515 expression expression NN 516 518 in in IN 519 527 response response NN 528 530 to to TO 531 535 IL-2 il-2 NN 536 538 in in IN 539 543 both both DT 544 550 T-cell t-cell NN 551 556 lines line NNS 557 560 and and CC 561 566 human human JJ 567 577 peripheral peripheral JJ 578 583 blood blood NN 584 595 lymphocytes lymphocyte NNS 595 596 . . . 597 603 SOCS-3 SOCS-3 NNP 604 611 protein protein NN 612 615 was be VBD 616 626 detectable detectable JJ 627 629 as as RB 630 635 early early RB 636 638 as as IN 639 641 30 30 CD 642 645 min min NN 646 655 following follow VBG 656 660 IL-2 il-2 NN 661 672 stimulation stimulation NN 672 673 , , , 674 679 while while IN 680 683 CIS CIS NNP 684 687 was be VBD 688 692 seen see VBN 693 697 only only RB 698 700 at at IN 701 704 low low JJ 705 711 levels level NNS 712 717 after after IN 718 719 2 2 CD 720 722 h. h. NN 723 729 Unlike unlike IN 730 733 CIS CIS NNP 733 734 , , , 735 741 SOCS-3 SOCS-3 NNP 742 745 was be VBD 746 753 rapidly rapidly RB 754 762 tyrosine tyrosine NN 763 777 phosphorylated phosphorylated JJ 778 780 in in IN 781 789 response response NN 790 792 to to TO 793 797 IL-2 il-2 NN 797 798 . . . 799 807 Tyrosine Tyrosine NNP 808 823 phosphorylation phosphorylation NN 824 826 of of IN 827 833 SOCS-3 SOCS-3 NNP 834 837 was be VBD 838 846 observed observe VBN 847 851 upon upon IN 852 864 coexpression coexpression NN 865 869 with with IN 870 874 Jak1 Jak1 NNP 875 878 and and CC 879 883 Jak2 Jak2 NNP 884 887 but but CC 888 892 only only RB 893 899 weakly weakly RB 900 904 with with IN 905 909 Jak3 Jak3 NNP 909 910 . . . 911 913 In in IN 914 919 these these DT 920 931 experiments experiment NNS 931 932 , , , 933 939 SOCS-3 SOCS-3 NNP 940 950 associated associate VBN 951 955 with with IN 956 960 Jak1 Jak1 NNP 961 964 and and CC 965 974 inhibited inhibit VBD 975 979 Jak1 jak1 NN 980 995 phosphorylation phosphorylation NN 995 996 , , , 997 1000 and and CC 1001 1005 this this DT 1006 1016 inhibition inhibition NN 1017 1020 was be VBD 1021 1029 markedly markedly RB 1030 1038 enhanced enhance VBN 1039 1041 by by IN 1042 1045 the the DT 1046 1054 presence presence NN 1055 1057 of of IN 1058 1062 IL-2 il-2 NN 1063 1071 receptor receptor NN 1072 1076 beta beta NN 1077 1082 chain chain NN 1083 1084 ( ( ( 1084 1093 IL-2Rbeta IL-2Rbeta NNP 1093 1094 ) ) ) 1094 1095 . . . 1096 1104 Moreover moreover RB 1104 1105 , , , 1106 1115 following follow VBG 1116 1120 IL-2 il-2 NN 1121 1132 stimulation stimulation NN 1133 1135 of of IN 1136 1137 T t NN 1138 1143 cells cell NNS 1143 1144 , , , 1145 1151 SOCS-3 SOCS-3 NNP 1152 1155 was be VBD 1156 1160 able able JJ 1161 1163 to to TO 1164 1172 interact interact VB 1173 1177 with with IN 1178 1181 the the DT 1182 1186 IL-2 il-2 NN 1187 1195 receptor receptor NN 1196 1203 complex complex NN 1203 1204 , , , 1205 1208 and and CC 1209 1211 in in IN 1212 1222 particular particular JJ 1223 1231 tyrosine tyrosine NN 1232 1246 phosphorylated phosphorylated JJ 1247 1251 Jak1 Jak1 NNP 1252 1255 and and CC 1256 1265 IL-2Rbeta IL-2Rbeta NNP 1265 1266 . . . 1267 1279 Additionally additionally RB 1279 1280 , , , 1281 1283 in in IN 1284 1295 lymphocytes lymphocyte NNS 1296 1306 expressing express VBG 1307 1313 SOCS-3 socs-3 NN 1314 1317 but but CC 1318 1321 not not RB 1322 1325 CIS CIS NNP 1325 1326 , , , 1327 1339 IL-2-induced il-2-induced JJ 1340 1348 tyrosine tyrosine NN 1349 1364 phosphorylation phosphorylation NN 1365 1367 of of IN 1368 1374 STAT5b STAT5b NNP 1375 1378 was be VBD 1379 1387 markedly markedly RB 1388 1395 reduced reduce VBN 1395 1396 , , , 1397 1402 while while IN 1403 1408 there there EX 1409 1412 was be VBD 1413 1417 only only RB 1418 1419 a a DT 1420 1424 weak weak JJ 1425 1431 effect effect NN 1432 1434 on on IN 1435 1448 IL-3-mediated il-3-mediated JJ 1449 1455 STAT5b STAT5b NNP 1456 1464 tyrosine tyrosine NN 1465 1480 phosphorylation phosphorylation NN 1480 1481 . . . 1482 1489 Finally finally RB 1489 1490 , , , 1491 1504 proliferation proliferation NN 1505 1512 induced induce VBN 1513 1515 by by IN 1516 1520 both both CC 1521 1526 IL-2- IL-2- NNP 1527 1530 and and CC 1531 1535 IL-3 IL-3 NNP 1536 1539 was be VBD 1540 1553 significantly significantly RB 1554 1563 inhibited inhibit VBN 1564 1566 in in IN 1567 1570 the the DT 1571 1579 presence presence NN 1580 1582 of of IN 1583 1589 SOCS-3 SOCS-3 NNP 1589 1590 . . . 1591 1594 The the DT 1595 1603 findings finding NNS 1604 1611 suggest suggest VBP 1612 1616 that that IN 1617 1621 when when WRB 1622 1628 SOCS-3 socs-3 NN 1629 1631 is be VBZ 1632 1639 rapidly rapidly RB 1640 1647 induced induce VBN 1648 1650 by by IN 1651 1655 IL-2 il-2 NN 1656 1658 in in IN 1659 1660 T t NN 1661 1666 cells cell NNS 1666 1667 , , , 1668 1670 it it PRP 1671 1675 acts act VBZ 1676 1678 to to TO 1679 1686 inhibit inhibit VB 1687 1691 IL-2 il-2 NN 1692 1701 responses response NNS 1702 1704 in in IN 1705 1706 a a DT 1707 1716 classical classical JJ 1717 1725 negative negative JJ 1726 1734 feedback feedback NN 1735 1739 loop loop NN 1739 1740 . . .