0 8 p70(s6k) p70(s6k) NNP 9 19 integrates integrate VBZ 20 40 phosphatidylinositol phosphatidylinositol NN 41 49 3-kinase 3-kinase NNP 50 53 and and CC 54 73 rapamycin-regulated rapamycin-regulated JJ 74 81 signals signal NNS 82 85 for for IN 86 89 E2F E2F NNP 90 100 regulation regulation NN 101 103 in in IN 104 105 T t NN 106 117 lymphocytes lymphocyte NNS 117 118 . . . 120 122 In in IN 123 124 T t NN 125 136 lymphocytes lymphocyte NNS 136 137 , , , 138 141 the the DT 142 155 hematopoietic hematopoietic JJ 156 164 cytokine cytokine NN 165 178 interleukin-2 interleukin-2 NN 179 180 ( ( ( 180 184 IL-2 il-2 NN 184 185 ) ) ) 186 190 uses use VBZ 191 211 phosphatidylinositol phosphatidylinositol NN 212 220 3-kinase 3-kinase NNP 221 222 ( ( ( 222 224 PI PI NNP 225 242 3-kinase)-induced 3-kinase)-induced JJ 243 252 signaling signaling NN 253 261 pathways pathway NNS 262 264 to to TO 265 273 regulate regulate VB 274 277 E2F E2F NNP 278 293 transcriptional transcriptional JJ 294 302 activity activity NN 302 303 , , , 304 305 a a DT 306 314 critical critical JJ 315 319 cell cell NN 320 325 cycle cycle NN 326 336 checkpoint checkpoint NN 336 337 . . . 338 340 PI pi NN 341 349 3-kinase 3-kinase NNP 350 354 also also RB 355 364 regulates regulate VBZ 365 368 the the DT 369 377 activity activity NN 378 380 of of IN 381 389 p70(s6k) p70(s6k) NNP 389 390 , , , 391 394 the the DT 395 398 40S 40s NN 399 408 ribosomal ribosomal JJ 409 416 protein protein NN 417 419 S6 S6 NNP 420 426 kinase kinase NNP 426 427 , , , 428 429 a a DT 430 438 response response NN 439 443 that that WDT 444 446 is be VBZ 447 456 abrogated abrogate VBN 457 459 by by IN 460 463 the the DT 464 473 macrolide macrolide NN 474 483 rapamycin rapamycin NN 483 484 . . . 485 489 This this DT 490 507 immunosuppressive immunosuppressive JJ 508 512 drug drug NN 513 515 is be VBZ 516 521 known know VBN 522 524 to to TO 525 532 prevent prevent VB 533 539 T-cell t-cell NN 540 553 proliferation proliferation NN 553 554 , , , 555 558 but but CC 559 562 the the DT 563 570 precise precise JJ 571 576 point point NN 577 579 at at IN 580 585 which which WDT 586 595 rapamycin rapamycin NN 596 605 regulates regulate VBZ 606 612 T-cell t-cell NN 613 618 cycle cycle NN 619 630 progression progression NN 631 634 has have VBZ 635 638 yet yet RB 639 641 to to TO 642 644 be be VB 645 655 elucidated elucidate VBN 655 656 . . . 657 665 Moreover moreover RB 665 666 , , , 667 670 the the DT 671 678 effects effect NNS 679 681 of of IN 682 691 rapamycin rapamycin NN 692 694 on on IN 694 695 , , , 696 699 and and CC 700 703 the the DT 704 708 role role NN 709 711 of of IN 712 720 p70(s6k) p70(s6k) NN 721 723 in in IN 723 724 , , , 725 729 IL-2 IL-2 NNP 730 733 and and CC 734 736 PI PI NNP 737 745 3-kinase 3-kinase NNP 746 756 activation activation NN 757 759 of of IN 760 764 E2Fs e2f NNS 765 769 have have VBP 770 773 not not RB 774 778 been be VBN 779 792 characterized characterize VBN 792 793 . . . 794 797 Our our PRP$ 798 805 present present JJ 806 813 results result NNS 814 818 show show VBP 819 823 that that IN 824 829 IL-2- IL-2- NNP 830 833 and and CC 834 836 PI PI NNP 837 853 3-kinase-induced 3-kinase-induced JJ 854 862 pathways pathway NNS 863 866 for for IN 867 870 the the DT 871 881 regulation regulation NN 882 884 of of IN 885 888 E2F E2F NNP 889 904 transcriptional transcriptional JJ 905 913 activity activity NN 914 921 include include VBP 922 926 both both CC 927 946 rapamycin-resistant rapamycin-resistant JJ 947 950 and and CC 951 970 rapamycin-sensitive rapamycin-sensitive JJ 971 981 components component NNS 981 982 . . . 983 993 Expression expression NN 994 996 of of IN 997 998 a a DT 999 1018 rapamycin-resistant rapamycin-resistant JJ 1019 1025 mutant mutant NN 1026 1028 of of IN 1029 1037 p70(s6k) p70(s6k) NN 1038 1040 in in IN 1041 1042 T t NN 1043 1048 cells cell NNS 1049 1054 could could MD 1055 1062 restore restore VB 1063 1083 rapamycin-suppressed rapamycin-suppressed JJ 1084 1087 E2F e2f NN 1088 1097 responses response NNS 1097 1098 . . . 1099 1103 Thus thus RB 1103 1104 , , , 1105 1108 the the DT 1109 1129 rapamycin-controlled rapamycin-controlled JJ 1130 1139 processes process NNS 1140 1148 involved involve VBN 1149 1151 in in IN 1152 1155 E2F E2F NNP 1156 1166 regulation regulation NN 1167 1173 appear appear VBP 1174 1176 to to TO 1177 1179 be be VB 1180 1188 mediated mediate VBN 1189 1191 by by IN 1192 1200 p70(s6k) p70(s6k) NNP 1200 1201 . . . 1202 1209 However however RB 1209 1210 , , , 1211 1214 the the DT 1215 1234 rapamycin-resistant rapamycin-resistant JJ 1235 1243 p70(s6k) p70(s6k) NN 1244 1249 could could MD 1250 1253 not not RB 1254 1260 rescue rescue VB 1261 1270 rapamycin rapamycin NN 1271 1281 inhibition inhibition NN 1282 1284 of of IN 1285 1291 T-cell t-cell NN 1292 1297 cycle cycle NN 1298 1303 entry entry NN 1303 1304 , , , 1305 1315 consistent consistent JJ 1316 1320 with with IN 1321 1324 the the DT 1325 1336 involvement involvement NN 1337 1339 of of IN 1340 1350 additional additional JJ 1350 1351 , , , 1352 1371 rapamycin-sensitive rapamycin-sensitive JJ 1372 1380 pathways pathway NNS 1381 1383 in in IN 1384 1387 the the DT 1388 1395 control control NN 1396 1398 of of IN 1399 1405 T-cell t-cell NN 1406 1411 cycle cycle NN 1412 1423 progression progression NN 1423 1424 . . . 1425 1428 The the DT 1429 1436 present present JJ 1437 1444 results result NNS 1445 1449 thus thus RB 1450 1454 show show VBP 1455 1459 that that IN 1460 1468 p70(s6k) p70(s6k) NN 1469 1471 is be VBZ 1472 1476 able able JJ 1477 1479 to to TO 1480 1488 regulate regulate VB 1489 1492 E2F E2F NNP 1493 1508 transcriptional transcriptional JJ 1509 1517 activity activity NN 1518 1521 and and CC 1522 1529 provide provide VBP 1530 1536 direct direct JJ 1537 1545 evidence evidence NN 1546 1549 for for IN 1550 1553 the the DT 1554 1559 first first JJ 1560 1564 time time NN 1565 1568 for for IN 1569 1570 a a DT 1571 1575 link link NN 1576 1583 between between IN 1584 1588 IL-2 il-2 NN 1589 1598 receptors receptor NNS 1598 1599 , , , 1600 1602 PI PI NNP 1603 1611 3-kinase 3-kinase NNP 1611 1612 , , , 1613 1616 and and CC 1617 1625 p70(s6k) p70(s6k) NNP 1626 1630 that that WDT 1631 1640 regulates regulate VBZ 1641 1642 a a DT 1643 1650 crucial crucial JJ 1651 1653 G1 g1 NN 1654 1664 checkpoint checkpoint NN 1665 1667 in in IN 1668 1669 T t NN 1670 1681 lymphocytes lymphocyte NNS 1681 1682 . . .