0 6 Signal Signal NNP 7 19 transduction transduction NN 20 28 pathways pathway NNS 29 31 in in IN 32 38 normal normal JJ 39 44 human human JJ 45 54 monocytes monocyte NNS 55 65 stimulated stimulate VBN 66 68 by by IN 69 78 cytokines cytokine NNS 79 82 and and CC 83 92 mediators mediator NNS 92 93 : : : 94 105 comparative comparative JJ 106 111 study study NN 112 116 with with IN 117 123 normal normal JJ 124 129 human human JJ 130 141 neutrophils neutrophil NNS 142 144 or or CC 145 156 transformed transform VBN 157 162 cells cell NNS 163 166 and and CC 167 170 the the DT 171 179 putative putative JJ 180 185 roles role NNS 186 188 in in IN 189 202 functionality functionality NN 203 206 and and CC 207 211 cell cell NN 212 219 biology biology NN 219 220 . . . 222 244 Granulocyte-macrophage granulocyte-macrophage JJ 245 263 colony-stimulating colony-stimulating JJ 264 270 factor factor NN 271 272 ( ( ( 272 278 GM-CSF GM-CSF NNP 278 279 ) ) ) 280 283 and and CC 284 295 interleukin interleukin NN 296 297 ( ( ( 297 299 IL IL NNP 299 300 ) ) ) 301 303 -3 -3 CD 304 311 induced induce VBD 312 320 tyrosine tyrosine NN 321 336 phosphorylation phosphorylation NN 337 339 of of IN 340 346 92-kDa 92-kda JJ 347 354 protein protein NN 355 357 in in IN 358 364 normal normal JJ 365 370 human human JJ 371 380 monocytes monocyte NNS 380 381 . . . 382 384 We we PRP 385 395 identified identify VBD 396 400 this this DT 401 407 92-kDa 92-kda JJ 408 415 protein protein NN 416 418 as as IN 419 424 STAT5 STAT5 NNP 424 425 , , , 426 429 but but CC 430 433 not not RB 434 436 as as IN 437 443 STATs1 STATs1 NNP 443 444 , , , 445 446 3 3 CD 446 447 , , , 448 451 and and CC 452 453 6 6 CD 454 457 nor nor CC 458 463 c-fes c-fes NN 464 467 and and CC 468 471 vav vav NN 472 485 protooncogene protooncogene NN 486 494 products product NNS 494 495 , , , 496 499 and and CC 500 512 demonstrated demonstrate VBD 513 516 its its PRP$ 517 530 translocation translocation NN 531 533 to to TO 534 537 the the DT 538 545 nucleus nucleus NN 545 546 , , , 547 558 enhancement enhancement NN 559 561 of of IN 562 570 specific specific JJ 571 574 DNA dna NN 575 582 binding binding NN 583 591 capacity capacity NN 591 592 , , , 593 596 and and CC 597 609 potentiation potentiation NN 610 612 of of IN 613 627 trancriptional trancriptional JJ 628 636 activity activity NN 637 639 by by IN 640 646 GM-CSF GM-CSF NNP 646 647 . . . 648 687 N-formyl-methionyl-leucyl-phenylalanine N-formyl-methionyl-leucyl-phenylalanine NNP 688 689 ( ( ( 689 693 FMLP FMLP NNP 693 694 ) ) ) 695 698 and and CC 699 706 phorbol phorbol NN 707 716 myristate myristate NN 717 724 acetate acetate NN 725 726 ( ( ( 726 729 PMA PMA NNP 729 730 ) ) ) 731 738 induced induce VBD 739 747 tyrosine tyrosine NN 748 763 phosphorylation phosphorylation NN 764 766 of of IN 767 770 42- 42- CD 771 774 and and CC 775 781 44-kDa 44-kda JJ 782 790 proteins protein NNS 790 791 , , , 792 797 which which WDT 798 802 were be VBD 803 813 identified identify VBN 814 816 as as IN 817 830 extracellular extracellular JJ 831 847 signal-regulated signal-regulated JJ 848 854 kinase kinase NNP 855 856 ( ( ( 856 859 ERK ERK NNP 859 860 ) ) ) 860 861 , , , 862 864 in in IN 865 870 human human JJ 871 880 monocytes monocyte NNS 880 881 . . . 882 884 In in IN 885 891 marked marked JJ 892 900 contrast contrast NN 901 903 to to TO 904 915 neutrophils neutrophil NNS 916 919 and and CC 920 924 MO7e mo7e NN 925 930 cells cell NNS 930 931 , , , 932 938 GM-CSF GM-CSF NNP 939 942 did do VBD 943 946 not not RB 947 953 induce induce VB 954 962 tyrosine tyrosine NN 963 978 phosphorylation phosphorylation NN 979 982 and and CC 983 993 activation activation NN 994 996 of of IN 997 1000 ERK ERK NNP 1001 1003 in in IN 1004 1013 monocytes monocyte NNS 1013 1014 . . . 1015 1020 Among among IN 1021 1029 upstream upstream JJ 1030 1039 signaling signal VBG 1040 1049 molecules molecule NNS 1050 1052 of of IN 1053 1056 ERK ERK NNP 1056 1057 , , , 1058 1061 Shc Shc NNP 1062 1065 was be VBD 1066 1080 constitutively constitutively RB 1081 1091 associated associate VBN 1092 1096 with with IN 1097 1101 Grb2 grb2 NN 1102 1105 and and CC 1106 1109 was be VBD 1110 1113 not not RB 1114 1137 tyrosine-phosphorylated tyrosine-phosphorylate VBN 1138 1140 by by IN 1141 1147 GM-CSF GM-CSF NNP 1148 1151 and and CC 1152 1156 FMLP FMLP NNP 1156 1157 , , , 1158 1161 and and CC 1162 1166 Sos1 Sos1 NNP 1167 1170 and and CC 1171 1178 c-Raf-1 c-raf-1 NN 1179 1183 were be VBD 1184 1187 not not RB 1188 1202 phosphorylated phosphorylate VBN 1203 1205 by by IN 1206 1212 GM-CSF GM-CSF NNP 1212 1213 , , , 1214 1218 IL-3 IL-3 NNP 1218 1219 , , , 1220 1223 TNF TNF NNP 1223 1224 , , , 1225 1228 and and CC 1229 1233 FMLP FMLP NNP 1234 1236 in in IN 1237 1246 monocytes monocyte NNS 1246 1247 , , , 1248 1255 whereas whereas IN 1256 1259 all all PDT 1260 1265 these these DT 1266 1275 signaling signal VBG 1276 1285 molecules molecule NNS 1286 1290 were be VBD 1291 1299 affected affect VBN 1300 1306 and/or and/or CC 1307 1315 utilized utilize VBN 1316 1318 by by IN 1319 1325 GM-CSF GM-CSF NNP 1326 1328 in in IN 1329 1333 MO7e MO7e NNP 1334 1339 cells cell NNS 1339 1340 . . . 1341 1343 In in IN 1344 1352 contrast contrast NN 1353 1355 to to TO 1356 1367 neutrophils neutrophil NNS 1367 1368 , , , 1369 1372 p38 p38 NN 1373 1376 was be VBD 1377 1391 constitutively constitutively RB 1392 1406 phosphorylated phosphorylate VBN 1407 1410 and and CC 1411 1428 agonist-dependent agonist-dependent JJ 1429 1444 phosphorylation phosphorylation NN 1445 1448 and and CC 1449 1459 activation activation NN 1460 1463 was be VBD 1464 1467 not not RB 1468 1476 detected detect VBN 1477 1479 in in IN 1480 1485 human human JJ 1486 1495 monocytes monocyte NNS 1495 1496 . . . 1497 1507 Superoxide Superoxide NNP 1508 1515 release release NN 1516 1526 stimulated stimulate VBN 1527 1529 by by IN 1530 1534 FMLP FMLP NNP 1535 1538 was be VBD 1539 1548 inhibited inhibit VBN 1549 1558 partially partially RB 1559 1561 by by IN 1562 1569 PD98059 PD98059 NNP 1570 1572 or or CC 1573 1581 SB203580 SB203580 NNP 1581 1582 , , , 1583 1584 a a DT 1585 1593 specific specific JJ 1594 1603 inhibitor inhibitor NN 1604 1606 of of IN 1607 1610 ERK ERK NNP 1611 1613 or or CC 1614 1617 p38 p38 NN 1618 1625 pathway pathway NN 1625 1626 , , , 1627 1630 and and CC 1631 1634 was be VBD 1635 1641 almost almost RB 1642 1652 completely completely RB 1653 1662 inhibited inhibit VBN 1663 1665 by by IN 1666 1669 the the DT 1670 1681 combination combination NN 1682 1684 of of IN 1685 1689 both both DT 1690 1700 inhibitors inhibitor NNS 1700 1701 , , , 1702 1709 whereas whereas IN 1710 1721 PMA-induced pma-induced JJ 1722 1732 superoxide superoxide NN 1733 1740 release release NN 1741 1744 was be VBD 1745 1754 resistant resistant JJ 1755 1757 to to TO 1758 1763 these these DT 1764 1767 two two CD 1768 1778 inhibitors inhibitor NNS 1779 1781 in in IN 1782 1791 monocytes monocyte NNS 1791 1792 . . . 1793 1800 PD98059 PD98059 NNP 1801 1810 inhibited inhibit VBD 1811 1827 GM-CSF-dependent gm-csf-dependent JJ 1828 1841 proliferation proliferation NN 1842 1844 of of IN 1845 1849 MO7e mo7e NN 1850 1855 cells cell NNS 1855 1856 . . . 1857 1864 Present present JJ 1865 1872 results result NNS 1873 1881 indicate indicate VBP 1882 1896 trancriptional trancriptional JJ 1897 1902 roles role NNS 1903 1905 of of IN 1906 1911 STAT5 stat5 NN 1912 1915 and and CC 1916 1926 functional functional JJ 1927 1932 roles role NNS 1933 1935 of of IN 1936 1939 ERK ERK NNP 1940 1946 and/or and/or CC 1947 1950 p38 p38 NN 1951 1953 in in IN 1954 1960 normal normal JJ 1961 1966 human human JJ 1967 1976 monocytes monocyte NNS 1977 1987 stimulated stimulate VBN 1988 1990 by by IN 1991 2004 physiological physiological JJ 2005 2022 receptor-mediated receptor-mediated JJ 2023 2031 agonists agonist NNS 2032 2038 GM-CSF GM-CSF NNP 2039 2042 and and CC 2043 2047 FMLP FMLP NNP 2047 2048 . . . 2049 2057 Possible possible JJ 2058 2063 roles role NNS 2064 2066 of of IN 2067 2070 ERK ERK NNP 2071 2073 in in IN 2074 2087 proliferation proliferation NN 2088 2090 of of IN 2091 2102 transformed transform VBN 2103 2108 cells cell NNS 2109 2113 were be VBD 2114 2118 also also RB 2119 2128 suggested suggest VBN 2128 2129 . . .