0 13 Extracellular extracellular JJ 14 30 signal-regulated signal-regulated JJ 31 38 protein protein NN 39 45 kinase kinase NNP 46 47 ( ( ( 47 61 ERK)-dependent erk)-dependent JJ 62 65 and and CC 66 81 ERK-independent erk-independent JJ 82 90 pathways pathway NNS 91 97 target target VBP 98 103 STAT3 stat3 NN 104 106 on on IN 107 117 serine-727 serine-727 NN 118 120 in in IN 121 126 human human JJ 127 138 neutrophils neutrophil NNS 139 149 stimulated stimulate VBN 150 152 by by IN 153 164 chemotactic chemotactic JJ 165 172 factors factor NNS 173 176 and and CC 177 186 cytokines cytokine NNS 186 187 . . . 189 194 STAT3 STAT3 NNP 195 196 ( ( ( 196 202 signal signal NN 203 213 transducer transducer NN 214 217 and and CC 218 227 activator activator NN 228 230 of of IN 231 244 transcription transcription NN 245 246 3 3 CD 246 247 ) ) ) 248 250 is be VBZ 251 252 a a DT 253 259 latent latent JJ 260 273 transcription transcription NN 274 280 factor factor NN 281 285 that that WDT 286 288 is be VBZ 289 298 activated activate VBN 299 301 by by IN 302 310 tyrosine tyrosine NN 311 326 phosphorylation phosphorylation NN 327 328 ( ( ( 328 335 Tyr-705 tyr-705 NN 335 336 ) ) ) 337 339 in in IN 340 345 cells cell NNS 346 356 stimulated stimulate VBN 357 361 with with IN 362 371 cytokines cytokine NNS 372 374 or or CC 375 381 growth growth NN 382 389 factors factor NNS 389 390 . . . 391 397 Recent recent JJ 398 405 studies study NNS 406 413 suggest suggest VBP 414 418 that that IN 419 422 one one CD 423 425 or or CC 426 430 more more JJR 431 442 cytoplasmic cytoplasmic JJ 443 449 serine serine NN 450 457 kinases kinase NNS 458 462 also also RB 463 476 phosphorylate phosphorylate VBP 477 482 STAT3 stat3 NN 483 486 and and CC 487 490 are be VBP 491 500 necessary necessary JJ 501 504 for for IN 505 512 maximal maximal JJ 513 517 gene gene NN 518 528 activation activation NN 528 529 . . . 530 534 Here here RB 535 537 we we PRP 538 549 demonstrate demonstrate VBP 549 550 , , , 551 555 with with IN 556 557 a a DT 558 571 site-specific site-specific JJ 572 580 antibody antibody NN 580 581 , , , 582 586 that that IN 587 592 STAT3 STAT3 NNP 593 595 is be VBZ 596 610 phosphorylated phosphorylate VBN 611 613 on on IN 614 621 Ser-727 ser-727 NN 622 624 in in IN 625 630 human human JJ 631 642 neutrophils neutrophil NNS 643 653 stimulated stimulate VBN 654 658 with with IN 659 670 chemotactic chemotactic JJ 671 678 factors factor NNS 679 680 ( ( ( 680 719 N-formyl-methionyl-leucyl-phenylalanine N-formyl-methionyl-leucyl-phenylalanine NNP 720 723 and and CC 724 734 complement complement NN 735 738 C5a C5a NNP 738 739 ) ) ) 739 740 , , , 741 750 cytokines cytokine NNS 751 752 [ [ ( 752 774 granulocyte/macrophage granulocyte/macrophage NN 775 793 colony-stimulating colony-stimulating JJ 794 800 factor factor NN 801 802 ( ( ( 802 808 GM-CSF GM-CSF NNP 808 809 ) ) ) 810 813 and and CC 814 825 granulocyte granulocyte NN 826 844 colony-stimulating colony-stimulating JJ 845 851 factor factor NN 852 853 ( ( ( 853 858 G-CSF G-CSF NNP 858 859 ) ) ) 859 860 ] ] ) 860 861 , , , 862 864 or or CC 865 866 a a DT 867 874 protein protein NN 875 881 kinase kinase NNP 882 883 C C NNP 884 893 activator activator NN 894 895 ( ( ( 895 900 PMA). PMA). NNP 901 902 ( ( ( 902 946 2-Amino-3’-methoxyphenyl)oxanaphthalen-4-one 2-Amino-3'-methoxyphenyl)oxanaphthalen-4-one NNP 947 948 ( ( ( 948 950 PD PD NNP 951 956 98059 98059 CD 956 957 ) ) ) 957 958 , , , 959 961 an an DT 962 971 inhibitor inhibitor NN 972 974 of of IN 975 988 extracellular extracellular JJ 989 1005 signal-regulated signal-regulated JJ 1006 1013 protein protein NN 1014 1020 kinase kinase NNP 1021 1022 ( ( ( 1022 1025 ERK ERK NNP 1025 1026 ) ) ) 1027 1037 activation activation NN 1037 1038 , , , 1039 1046 blocked block VBD 1047 1050 the the DT 1051 1057 serine serine NN 1058 1073 phosphorylation phosphorylation NN 1074 1076 of of IN 1077 1082 STAT3 STAT3 NNP 1083 1090 induced induce VBN 1091 1093 by by IN 1094 1105 chemotactic chemotactic JJ 1106 1113 factors factor NNS 1114 1116 or or CC 1117 1120 PMA PMA NNP 1120 1121 . . . 1122 1125 The the DT 1126 1130 drug drug NN 1131 1134 was be VBD 1135 1139 less less RBR 1140 1149 effective effective JJ 1150 1152 on on IN 1153 1162 cytokines cytokine NNS 1162 1163 : : : 1164 1166 it it PRP 1167 1176 virtually virtually RB 1177 1186 abolished abolish VBD 1187 1190 the the DT 1191 1199 response response NN 1200 1202 to to TO 1203 1209 GM-CSF GM-CSF NNP 1210 1214 that that WDT 1215 1223 occurred occur VBD 1224 1225 5 5 CD 1226 1229 min min NN 1230 1235 after after IN 1236 1247 stimulation stimulation NN 1248 1251 but but CC 1252 1256 only only RB 1257 1263 partly partly RB 1264 1273 decreased decrease VBD 1274 1279 those those DT 1280 1282 at at IN 1283 1288 15-30 15-30 CD 1289 1292 min min NN 1293 1296 and and CC 1297 1300 did do VBD 1301 1304 not not RB 1305 1316 appreciably appreciably RB 1317 1322 alter alter VB 1323 1332 responses response NNS 1333 1335 to to TO 1336 1341 G-CSF G-CSF NNP 1342 1352 regardless regardless RB 1353 1355 of of IN 1356 1366 incubation incubation NN 1367 1371 time time NN 1371 1372 . . . 1373 1420 1-(5-Isoquinolinylsulphonyl)-2-methylpiperazine 1-(5-isoquinolinylsulphonyl)-2-methylpiperazine NN 1421 1436 dihydrochloride dihydrochloride NN 1437 1438 ( ( ( 1438 1440 H7 H7 NNP 1440 1441 ) ) ) 1441 1442 , , , 1443 1445 an an DT 1446 1455 inhibitor inhibitor NN 1456 1458 of of IN 1459 1460 a a DT 1461 1469 putative putative JJ 1470 1475 STAT3 stat3 NN 1476 1482 serine serine NN 1483 1489 kinase kinase NNP 1489 1490 , , , 1491 1494 and and CC 1495 1555 4-(4-fluorophenyl)-2-(4-methylsulphinylphenyl)-5-(4-pyridyl) 4-(4-fluorophenyl)-2-(4-methylsulphinylphenyl)-5-(4-pyridyl) NNP 1556 1568 1H-imidazole 1H-imidazole NNP 1569 1570 ( ( ( 1570 1572 SB SB NNP 1573 1579 203580 203580 CD 1579 1580 ) ) ) 1580 1581 , , , 1582 1584 an an DT 1585 1594 inhibitor inhibitor NN 1595 1597 of of IN 1598 1601 p38 p38 NN 1602 1619 mitogen-activated mitogen-activated JJ 1620 1627 protein protein NN 1628 1629 ( ( ( 1629 1632 MAP MAP NNP 1632 1633 ) ) ) 1634 1640 kinase kinase NNP 1640 1641 , , , 1642 1645 did do VBD 1646 1649 not not RB 1650 1656 dampen dampen VB 1657 1660 any any DT 1661 1663 of of IN 1664 1669 these these DT 1670 1676 serine serine NN 1677 1692 phosphorylation phosphorylation NN 1693 1702 responses response NNS 1702 1703 . . . 1704 1706 We we PRP 1707 1714 propose propose VBP 1715 1719 that that IN 1720 1731 neutrophils neutrophil NNS 1732 1735 use use VBP 1736 1740 both both CC 1741 1754 ERK-dependent erk-dependent JJ 1755 1758 and and CC 1759 1774 ERK-independent erk-independent JJ 1775 1783 pathways pathway NNS 1784 1786 to to TO 1787 1800 phosphorylate phosphorylate VB 1801 1808 Ser-727 ser-727 NN 1809 1811 on on IN 1812 1817 STAT3 STAT3 NNP 1817 1818 . . . 1819 1822 The the DT 1823 1829 former former JJ 1830 1837 pathway pathway NN 1838 1840 is be VBZ 1841 1850 recruited recruit VBN 1851 1853 by by IN 1854 1857 all all DT 1858 1872 ERK-activating erk-activating JJ 1873 1880 stimuli stimulus NNS 1880 1881 , , , 1882 1889 whereas whereas IN 1890 1893 the the DT 1894 1900 latter latter JJ 1901 1908 pathway pathway NN 1909 1913 uses use VBZ 1914 1916 an an DT 1917 1926 undefined undefined JJ 1927 1933 serine serine NN 1934 1940 kinase kinase NNP 1941 1944 and and CC 1945 1947 is be VBZ 1948 1957 recruited recruit VBN 1958 1969 selectively selectively RB 1970 1972 by by IN 1973 1982 cytokines cytokine NNS 1982 1983 . . .