0 10 Activation Activation NNP 11 13 of of IN 14 19 early early JJ 20 26 growth growth NN 27 35 response response NN 36 37 1 1 CD 38 42 gene gene NN 43 56 transcription transcription NN 57 60 and and CC 61 68 pp90rsk pp90rsk NN 69 75 during during IN 76 85 induction induction NN 86 88 of of IN 89 98 monocytic monocytic JJ 99 114 differentiation differentiation NN 114 115 . . . 117 120 The the DT 121 128 present present JJ 129 133 work work NN 134 137 has have VBZ 138 145 studied study VBN 146 156 mechanisms mechanism NNS 157 168 responsible responsible JJ 169 172 for for IN 173 182 induction induction NN 183 185 of of IN 186 191 early early JJ 192 198 growth growth NN 199 207 response response NN 208 209 1 1 CD 210 211 ( ( ( 211 216 EGR-1 egr-1 NN 216 217 ) ) ) 218 222 gene gene NN 223 233 expression expression NN 234 240 during during IN 241 250 monocytic monocytic JJ 251 266 differentiation differentiation NN 267 269 of of IN 270 275 U-937 u-937 NN 276 283 myeloid myeloid JJ 284 292 leukemia leukemia NN 293 298 cells cell NNS 298 299 . . . 300 315 Differentiation Differentiation NNP 316 318 of of IN 319 324 U-937 u-937 NN 325 330 cells cell NNS 331 335 with with IN 336 372 12-O-tetradecanoylphorbol-13-acetate 12-O-tetradecanoylphorbol-13-acetate NNP 373 374 ( ( ( 374 377 TPA TPA NNP 377 378 ) ) ) 378 379 , , , 380 382 an an DT 383 392 activator activator NN 393 395 of of IN 396 399 the the DT 400 416 serine/threonine serine/threonine NN 417 424 protein protein NN 425 431 kinase kinase NNP 432 433 C C NNP 433 434 , , , 435 438 was be VBD 439 449 associated associate VBN 450 454 with with IN 455 470 transcriptional transcriptional JJ 471 481 activation activation NN 482 484 of of IN 485 490 EGR-1 egr-1 NN 491 508 promoter-reporter promoter-reporter JJ 509 519 constructs construct NNS 519 520 . . . 521 524 The the DT 525 530 EGR-1 egr-1 NN 531 539 promoter promoter NN 540 548 contains contain VBZ 549 552 six six CD 553 563 CC(A/T)6GG cc(a/t)6gg NN 564 565 ( ( ( 565 569 CArG CArG NNP 569 570 ) ) ) 571 577 motifs motif NNS 577 578 . . . 579 582 The the DT 583 586 two two CD 587 594 5’-most 5'-most JJ 595 601 distal distal JJ 602 606 CArG carg NN 607 616 sequences sequence NNS 617 626 conferred confer VBD 627 630 TPA TPA NNP 631 643 inducibility inducibility NN 643 644 . . . 645 647 In in IN 648 656 contrast contrast NN 656 657 , , , 658 663 there there EX 664 667 was be VBD 668 674 little little JJ 675 681 effect effect NN 682 684 of of IN 685 688 TPA TPA NNP 689 691 on on IN 692 697 EGR-1 egr-1 NN 698 711 transcription transcription NN 712 714 in in IN 715 716 a a DT 717 730 TPA-resistant tpa-resistant JJ 731 736 U-937 u-937 NN 737 741 cell cell NN 742 749 variant variant NN 749 750 , , , 751 761 designated designate VBN 762 765 TUR TUR NNP 765 766 . . . 767 776 Treatment Treatment NNP 777 779 of of IN 780 784 both both CC 785 790 U-937 u-937 NN 791 794 and and CC 795 798 TUR tur NN 799 804 cells cell NNS 805 809 with with IN 810 817 okadaic okadaic JJ 818 822 acid acid NN 822 823 , , , 824 826 an an DT 827 836 inhibitor inhibitor NN 837 839 of of IN 840 856 serine/threonine serine/threonine NN 857 864 protein protein NN 865 877 phosphatases phosphatas NNS 878 879 1 1 CD 880 883 and and CC 884 886 2A 2a NN 886 887 , , , 888 891 was be VBD 892 902 associated associate VBN 903 907 with with IN 908 917 induction induction NN 918 920 of of IN 921 930 monocytic monocytic JJ 931 946 differentiation differentiation NN 947 950 and and CC 951 956 EGR-1 egr-1 NN 957 970 transcription transcription NN 971 978 through through IN 979 982 the the DT 983 990 5’-most 5'-most JJ 991 995 CArG carg NN 996 1003 element element NN 1003 1004 . . . 1005 1010 Since since IN 1011 1016 these these DT 1017 1025 findings finding NNS 1026 1035 supported support VBD 1036 1039 the the DT 1040 1051 involvement involvement NN 1052 1054 of of IN 1055 1071 serine/threonine serine/threonine NN 1072 1079 protein protein NN 1080 1095 phosphorylation phosphorylation NN 1096 1098 in in IN 1099 1102 the the DT 1103 1113 regulation regulation NN 1114 1116 of of IN 1117 1122 EGR-1 egr-1 NN 1123 1133 expression expression NN 1133 1134 , , , 1135 1137 we we PRP 1138 1145 studied study VBD 1146 1156 activation activation NN 1157 1159 of of IN 1160 1163 the the DT 1164 1167 40S 40s NN 1168 1177 ribosomal ribosomal JJ 1178 1185 protein protein NN 1186 1188 S6 s6 NN 1189 1205 serine/threonine serine/threonine NN 1206 1213 kinases kinase NNS 1213 1214 , , , 1215 1222 pp70S6K pp70s6k NN 1223 1226 and and CC 1227 1234 pp90rsk pp90rsk NN 1234 1235 . . . 1236 1244 Although although IN 1245 1249 both both DT 1250 1257 kinases kinase NNS 1258 1269 participate participate VBP 1270 1272 in in IN 1273 1283 regulating regulate VBG 1284 1288 cell cell NN 1289 1295 growth growth NN 1295 1296 , , , 1297 1302 there there EX 1303 1306 was be VBD 1307 1309 no no DT 1310 1320 detectable detectable JJ 1321 1331 activation activation NN 1332 1334 of of IN 1335 1342 pp70S6K pp70s6k NN 1343 1349 during during IN 1350 1354 TPA- tpa- NN 1355 1357 or or CC 1358 1365 okadaic okadaic JJ 1366 1378 acid-induced acid-induced JJ 1379 1388 monocytic monocytic JJ 1389 1404 differentiation differentiation NN 1404 1405 . . . 1406 1414 Moreover moreover RB 1414 1415 , , , 1416 1425 rapamycin rapamycin NN 1425 1426 , , , 1427 1429 an an DT 1430 1439 inhibitor inhibitor NN 1440 1442 of of IN 1443 1450 pp70S6K pp70s6k NN 1451 1461 activation activation NN 1461 1462 , , , 1463 1466 had have VBD 1467 1469 no no DT 1470 1476 effect effect NN 1477 1479 on on IN 1480 1489 induction induction NN 1490 1492 of of IN 1493 1498 EGR-1 egr-1 NN 1499 1509 expression expression NN 1509 1510 . . . 1511 1513 In in IN 1514 1522 contrast contrast NN 1522 1523 , , , 1524 1532 analysis analysis NN 1533 1535 of of IN 1536 1543 pp90rsk pp90rsk NN 1544 1552 activity activity NN 1553 1555 by by IN 1556 1571 phosphorylation phosphorylation NN 1572 1574 of of IN 1575 1576 a a DT 1577 1584 peptide peptide NN 1585 1592 derived derive VBN 1593 1597 from from IN 1598 1600 S6 S6 NNP 1601 1608 protein protein NN 1609 1621 demonstrated demonstrate VBD 1622 1633 stimulation stimulation NN 1634 1636 of of IN 1637 1641 this this DT 1642 1648 kinase kinase NNP 1649 1651 in in IN 1652 1663 TPA-treated tpa-treated JJ 1664 1669 U-937 u-937 NN 1669 1670 , , , 1671 1674 and and CC 1675 1678 not not RB 1679 1682 TUR TUR NNP 1682 1683 , , , 1684 1689 cells cell NNS 1689 1690 . . . 1691 1698 Okadaic okadaic JJ 1699 1703 acid acid NN 1704 1713 treatment treatment NN 1714 1716 of of IN 1717 1721 both both DT 1722 1726 cell cell NN 1727 1732 types type NNS 1733 1736 was be VBD 1737 1747 associated associate VBN 1748 1752 with with IN 1753 1763 activation activation NN 1764 1766 of of IN 1767 1774 pp90rsk pp90rsk NN 1774 1775 . . .