0 17 Integrin-mediated integrin-mediated JJ 18 26 tyrosine tyrosine NN 27 42 phosphorylation phosphorylation NN 43 46 and and CC 47 55 cytokine cytokine NN 56 63 message message NN 64 73 induction induction NN 74 76 in in IN 77 86 monocytic monocytic JJ 87 92 cells cell NNS 92 93 . . . 94 95 A a DT 96 104 possible possible JJ 105 114 signaling signaling NN 115 119 role role NN 120 123 for for IN 124 127 the the DT 128 131 Syk Syk NNP 132 140 tyrosine tyrosine NN 141 147 kinase kinase NNP 147 148 . . . 150 160 Activation Activation NNP 161 163 of of IN 164 175 cytoplasmic cytoplasmic JJ 176 184 tyrosine tyrosine NN 185 192 kinases kinase NNS 193 195 is be VBZ 196 198 an an DT 199 208 important important JJ 209 215 aspect aspect NN 216 218 of of IN 219 225 signal signal NN 226 238 transduction transduction NN 239 247 mediated mediate VBN 248 250 by by IN 251 260 integrins integrin NNS 260 261 . . . 262 264 In in IN 265 268 the the DT 269 274 human human JJ 275 284 monocytic monocytic JJ 285 289 cell cell NN 290 294 line line NN 295 300 THP-1 thp-1 NN 300 301 , , , 302 308 either either CC 309 327 integrin-dependent integrin-dependent JJ 328 332 cell cell NN 333 341 adhesion adhesion NN 342 344 to to TO 345 356 fibronectin fibronectin NN 357 359 or or CC 360 368 ligation ligation NN 369 371 of of IN 372 376 beta beta SYM 377 378 1 1 CD 379 388 integrins integrin NNS 389 393 with with IN 394 404 antibodies antibody NNS 405 411 causes cause VBZ 412 413 a a DT 414 419 rapid rapid JJ 420 423 and and CC 424 431 intense intense JJ 432 440 tyrosine tyrosine NN 441 456 phosphorylation phosphorylation NN 457 459 of of IN 460 463 two two CD 464 468 sets set NNS 469 471 of of IN 472 480 proteins protein NNS 481 483 of of IN 484 489 about about RB 490 495 65-75 65-75 CD 496 499 and and CC 500 507 120-125 120-125 CD 508 511 kDa kda NN 511 512 . . . 513 515 In in IN 516 524 addition addition NN 524 525 , , , 526 534 integrin integrin NN 535 543 ligation ligation NN 544 549 leads lead VBZ 550 552 to to TO 553 560 nuclear nuclear JJ 561 574 translocation translocation NN 575 577 of of IN 578 581 the the DT 582 585 p50 p50 NN 586 589 and and CC 590 593 p65 p65 NN 594 602 subunits subunit NNS 603 605 of of IN 606 609 the the DT 610 618 NF-kappa NF-kappa NNP 619 620 B B NNP 621 634 transcription transcription NN 635 641 factor factor NN 641 642 , , , 643 645 to to TO 646 656 activation activation NN 657 659 of of IN 660 661 a a DT 662 670 reporter reporter NN 671 675 gene gene NN 676 682 driven drive VBN 683 685 by by IN 686 687 a a DT 688 696 promoter promoter NN 697 707 containing contain VBG 708 716 NF-kappa NF-kappa NNP 717 718 B B NNP 719 724 sites site NNS 724 725 , , , 726 729 and and CC 730 732 to to TO 733 742 increased increase VBN 743 749 levels level NNS 750 752 of of IN 753 758 mRNAs mrna NNS 759 762 for for IN 763 778 immediate-early immediate-early JJ 779 784 genes gene NNS 784 785 , , , 786 795 including include VBG 796 799 the the DT 800 808 cytokine cytokine NN 809 820 interleukin interleukin NN 821 822 ( ( ( 822 827 IL)-1 il)-1 NN 828 832 beta beta NN 832 833 . . . 834 837 The the DT 838 846 tyrosine tyrosine NN 847 853 kinase kinase NNP 854 864 inhibitors inhibitor NNS 865 874 genistein genistein NN 875 878 and and CC 879 889 herbimycin herbimycin NN 890 891 A a NN 892 897 block block VBP 898 902 both both CC 903 920 integrin-mediated integrin-mediated JJ 921 929 tyrosine tyrosine NN 930 945 phosphorylation phosphorylation NN 946 949 and and CC 950 959 increases increase NNS 960 962 in in IN 963 967 IL-1 il-1 NN 968 972 beta beta NN 973 980 message message NN 981 987 levels level NNS 987 988 , , , 989 999 indicating indicate VBG 1000 1001 a a DT 1002 1008 causal causal JJ 1009 1021 relationship relationship NN 1022 1029 between between IN 1030 1033 the the DT 1034 1037 two two CD 1038 1044 events event NNS 1044 1045 . . . 1046 1049 The the DT 1050 1060 components component NNS 1061 1069 tyrosine tyrosine NN 1070 1084 phosphorylated phosphorylated JJ 1085 1095 subsequent subsequent JJ 1096 1098 to to TO 1099 1103 cell cell NN 1104 1112 adhesion adhesion NN 1113 1120 include include VBP 1121 1129 paxillin paxillin NN 1129 1130 , , , 1131 1139 pp125FAK pp125fak NN 1139 1140 , , , 1141 1144 and and CC 1145 1148 the the DT 1149 1152 SH2 sh2 NN 1153 1159 domain domain NN 1160 1170 containing contain VBG 1171 1179 tyrosine tyrosine NN 1180 1186 kinase kinase NNP 1187 1190 Syk Syk NNP 1190 1191 . . . 1192 1194 In in IN 1195 1203 contrast contrast NN 1203 1204 , , , 1205 1213 integrin integrin NN 1214 1222 ligation ligation NN 1223 1227 with with IN 1228 1238 antibodies antibody NNS 1239 1246 induces induce VBZ 1247 1255 tyrosine tyrosine NN 1256 1271 phosphorylation phosphorylation NN 1272 1274 of of IN 1275 1278 Syk Syk NNP 1279 1282 but but CC 1283 1286 not not RB 1287 1289 of of IN 1290 1293 FAK FAK NNP 1294 1296 or or CC 1297 1305 paxillin paxillin NN 1305 1306 . . . 1307 1309 In in IN 1310 1318 adhering adhering JJ 1319 1324 cells cell NNS 1324 1325 , , , 1326 1339 pre-treatment pre-treatment NN 1340 1344 with with IN 1345 1357 cytochalasin cytochalasin NN 1358 1359 D D NNP 1360 1370 suppresses suppress VBZ 1371 1379 tyrosine tyrosine NN 1380 1395 phosphorylation phosphorylation NN 1396 1398 of of IN 1399 1402 FAK FAK NNP 1403 1406 and and CC 1407 1415 paxillin paxillin NN 1416 1419 but but CC 1420 1423 not not RB 1424 1426 of of IN 1427 1430 Syk Syk NNP 1430 1431 , , , 1432 1437 while while IN 1438 1442 IL-1 il-1 NN 1443 1447 beta beta NN 1448 1455 message message NN 1456 1465 induction induction NN 1466 1468 is be VBZ 1469 1479 unaffected unaffected JJ 1479 1480 . . . 1481 1486 These these DT 1487 1499 observations observation NNS 1500 1508 indicate indicate VBP 1509 1513 that that IN 1514 1517 the the DT 1518 1521 Syk Syk NNP 1522 1530 tyrosine tyrosine NN 1531 1537 kinase kinase NNP 1538 1541 may may MD 1542 1544 be be VB 1545 1547 an an DT 1548 1557 important important JJ 1558 1567 component component NN 1568 1570 of of IN 1571 1573 an an DT 1574 1582 integrin integrin NN 1583 1592 signaling signaling NN 1593 1600 pathway pathway NN 1601 1603 in in IN 1604 1613 monocytic monocytic JJ 1614 1619 cells cell NNS 1619 1620 , , , 1621 1628 leading lead VBG 1629 1631 to to TO 1632 1642 activation activation NN 1643 1645 of of IN 1646 1654 NF-kappa NF-kappa NNP 1655 1656 B B NNP 1657 1660 and and CC 1661 1663 to to TO 1664 1673 increased increase VBN 1674 1680 levels level NNS 1681 1683 of of IN 1684 1692 cytokine cytokine NN 1693 1701 messages message NNS 1701 1702 . . .