0 8 Thrombin Thrombin NNP 9 12 and and CC 13 21 thrombin thrombin NN 22 30 receptor receptor NN 31 38 agonist agonist NN 39 46 peptide peptide NN 47 53 induce induce VBP 54 59 early early JJ 60 66 events event NNS 67 69 of of IN 70 71 T t NN 72 76 cell cell NN 77 87 activation activation NN 88 91 and and CC 92 101 synergize synergize VB 102 106 with with IN 107 110 TCR TCR NNP 111 124 cross-linking cross-linking NN 125 128 for for IN 129 133 CD69 CD69 NNP 134 144 expression expression NN 145 148 and and CC 149 160 interleukin interleukin NN 161 162 2 2 CD 163 173 production production NN 173 174 . . . 176 184 Thrombin Thrombin NNP 185 196 stimulation stimulation NN 197 199 of of IN 200 203 the the DT 204 205 T t NN 206 214 leukemic leukemic JJ 215 219 cell cell NN 220 224 line line NN 225 231 Jurkat Jurkat NNP 232 239 induced induce VBD 240 241 a a DT 242 251 transient transient JJ 252 260 increase increase NN 261 263 in in IN 264 265 [ [ ( 265 272 Ca2+]i. Ca2+]i. NNP 273 284 Proteolytic proteolytic JJ 285 293 activity activity NN 294 296 of of IN 297 300 the the DT 301 307 enzyme enzyme NN 308 311 was be VBD 312 320 required require VBN 321 324 for for IN 325 329 this this DT 330 336 effect effect NN 337 342 since since IN 343 354 diisopropyl diisopropyl NN 355 379 fluorophosphate-thrombin fluorophosphate-thrombin NN 380 386 failed fail VBD 387 389 to to TO 390 398 increase increase VB 399 400 [ [ ( 400 407 Ca2+]i. Ca2+]i. NNP 408 419 Furthermore furthermore RB 419 420 , , , 421 428 hirudin hirudin NN 429 432 and and CC 433 446 anti-thrombin anti-thrombin NN 447 450 III iii CD 451 460 inhibited inhibit VBD 461 464 the the DT 465 481 thrombin-induced thrombin-induced JJ 482 483 [ [ ( 483 489 Ca2+]i Ca2+]i NNP 490 494 rise rise NN 495 497 in in IN 498 504 Jurkat Jurkat NNP 505 506 T t NN 507 512 cells cell NNS 512 513 . . . 514 515 A a DT 516 525 synthetic synthetic JJ 526 534 thrombin thrombin NN 535 543 receptor receptor NN 544 551 agonist agonist NN 552 559 peptide peptide NN 560 561 ( ( ( 561 564 TRP TRP NNP 564 565 ) ) ) 566 568 of of IN 569 570 7 7 CD 571 579 residues residue NNS 580 581 ( ( ( 581 588 SFLLRNP SFLLRNP NNP 588 589 ) ) ) 590 593 was be VBD 594 599 found find VBN 600 602 to to TO 603 605 be be VB 606 608 as as RB 609 618 effective effective JJ 619 621 as as IN 622 630 thrombin thrombin NN 631 634 for for IN 635 636 [ [ ( 636 642 Ca2+]i Ca2+]i NNP 643 655 mobilization mobilization NN 655 656 , , , 657 660 and and CC 661 665 both both DT 666 674 agonists agonist NNS 675 682 induced induce VBD 683 687 Ca2+ ca2+ NN 688 695 release release NN 696 707 exclusively exclusively RB 708 712 from from IN 713 721 internal internal JJ 722 728 stores store NNS 728 729 . . . 730 738 Thrombin Thrombin NNP 739 749 stimulated stimulate VBD 750 758 tyrosine tyrosine NN 759 774 phosphorylation phosphorylation NN 775 777 of of IN 778 785 several several JJ 786 794 proteins protein NNS 795 797 of of IN 798 807 molecular molecular JJ 808 812 mass mass NN 813 815 40 40 CD 815 816 , , , 817 819 42 42 CD 819 820 , , , 821 823 70 70 CD 823 824 , , , 825 828 120 120 CD 828 829 , , , 830 833 and and CC 834 837 130 130 CD 838 841 kDa kda NN 841 842 . . . 843 848 There there EX 849 852 was be VBD 853 854 a a DT 855 859 good good JJ 860 871 correlation correlation NN 872 879 between between IN 880 896 thrombin-induced thrombin-induced JJ 897 905 tyrosine tyrosine NN 906 921 phosphorylation phosphorylation NN 922 924 of of IN 925 928 the the DT 929 935 latter latter JJ 936 941 three three CD 942 950 proteins protein NNS 951 954 and and CC 955 959 Ca2+ ca2+ NN 960 972 mobilization mobilization NN 972 973 . . . 974 982 Thrombin Thrombin NNP 983 986 and and CC 987 990 TRP TRP NNP 991 995 also also RB 996 1002 caused cause VBD 1003 1016 translocation translocation NN 1017 1019 of of IN 1020 1027 protein protein NN 1028 1034 kinase kinase NNP 1035 1036 C C NNP 1037 1041 from from IN 1042 1045 the the DT 1046 1053 cytosol cytosol NN 1054 1056 to to TO 1057 1060 the the DT 1061 1067 plasma plasma NN 1068 1076 membrane membrane NN 1076 1077 . . . 1078 1080 As as IN 1081 1082 a a DT 1083 1089 likely likely JJ 1090 1101 consequence consequence NN 1102 1104 of of IN 1105 1110 these these DT 1111 1117 events event NNS 1117 1118 , , , 1119 1127 thrombin thrombin NN 1128 1137 activated activate VBD 1138 1141 the the DT 1142 1149 nuclear nuclear JJ 1150 1156 factor factor NN 1157 1162 NF-kB nf-kb NN 1162 1163 . . . 1164 1171 Several several JJ 1172 1176 cell cell NN 1177 1182 lines line NNS 1183 1185 of of IN 1186 1199 hematopoietic hematopoietic JJ 1200 1206 origin origin NN 1207 1216 including include VBG 1217 1220 the the DT 1221 1229 leukemic leukemic JJ 1230 1231 T t NN 1232 1236 cell cell NN 1237 1241 line line NN 1242 1249 HPB.ALL hpb.all NN 1250 1253 and and CC 1254 1257 the the DT 1258 1273 erythroleukemic erythroleukemic JJ 1274 1278 cell cell NN 1279 1283 line line NN 1284 1288 K562 k562 NN 1289 1293 were be VBD 1294 1304 responsive responsive JJ 1305 1307 to to TO 1308 1316 thrombin thrombin NN 1316 1317 , , , 1318 1325 whereas whereas IN 1326 1332 others other NNS 1333 1337 such such JJ 1338 1340 as as IN 1341 1345 THP1 THP1 NNP 1345 1346 , , , 1347 1348 a a DT 1349 1363 myelomonocytic myelomonocytic JJ 1364 1368 cell cell NN 1369 1373 line line NN 1373 1374 , , , 1375 1378 and and CC 1379 1382 BL2 BL2 NNP 1382 1383 , , , 1384 1385 a a DT 1386 1393 Burkitt Burkitt NNP 1394 1402 lymphoma lymphoma NN 1403 1407 were be VBD 1408 1418 refractory refractory JJ 1419 1421 to to TO 1422 1430 thrombin thrombin NN 1431 1433 or or CC 1434 1437 TRP TRP NNP 1438 1449 stimulation stimulation NN 1449 1450 . . . 1451 1454 The the DT 1455 1464 magnitude magnitude NN 1465 1467 of of IN 1468 1471 the the DT 1472 1480 thrombin thrombin NN 1481 1489 response response NN 1490 1492 in in IN 1493 1496 the the DT 1497 1506 different different JJ 1507 1511 cell cell NN 1512 1517 types type NNS 1518 1528 paralleled parallel VBD 1529 1532 the the DT 1533 1543 expression expression NN 1544 1546 of of IN 1547 1550 the the DT 1551 1559 thrombin thrombin NN 1560 1568 receptor receptor NN 1569 1573 mRNA mrna NN 1573 1574 . . . 1575 1577 We we PRP 1578 1583 found find VBD 1584 1588 that that IN 1589 1599 activation activation NN 1600 1602 of of IN 1603 1609 Jurkat Jurkat NNP 1610 1611 T t NN 1612 1617 cells cell NNS 1618 1620 by by IN 1621 1622 a a DT 1623 1634 combination combination NN 1635 1637 of of IN 1638 1656 phytohemagglutinin phytohemagglutinin NN 1657 1660 and and CC 1661 1668 phorbol phorbol NN 1669 1681 12-myristate 12-myristate NN 1682 1692 13-acetate 13-acetate NN 1693 1696 led lead VBD 1697 1699 to to TO 1700 1701 a a DT 1702 1710 dramatic dramatic JJ 1711 1721 inhibition inhibition NN 1722 1724 of of IN 1725 1733 thrombin thrombin NN 1734 1742 receptor receptor NN 1743 1747 mRNA mrna NN 1748 1758 expression expression NN 1759 1762 and and CC 1763 1765 to to TO 1766 1767 a a DT 1768 1779 concomitant concomitant JJ 1780 1784 loss loss NN 1785 1787 of of IN 1788 1791 the the DT 1792 1800 thrombin thrombin NN 1801 1809 response response NN 1809 1810 . . . 1811 1818 Finally finally RB 1818 1819 , , , 1820 1822 we we PRP 1823 1834 demonstrate demonstrate VBP 1835 1839 that that IN 1840 1848 thrombin thrombin NN 1849 1852 and and CC 1853 1856 TRP TRP NNP 1857 1865 enhanced enhance VBD 1866 1870 CD69 cd69 NN 1871 1881 expression expression NN 1882 1885 and and CC 1886 1897 interleukin interleukin NN 1898 1899 2 2 CD 1900 1910 production production NN 1911 1918 induced induce VBN 1919 1921 by by IN 1922 1923 T t NN 1924 1928 cell cell NN 1929 1937 receptor receptor NN 1938 1951 cross-linking cross-linking NN 1952 1954 in in IN 1955 1959 both both CC 1960 1966 Jurkat Jurkat NNP 1967 1968 T t NN 1969 1974 cells cell NNS 1975 1978 and and CC 1979 1989 peripheral peripheral JJ 1990 1995 blood blood NN 1996 2007 lymphocytes lymphocyte NNS 2007 2008 . . . 2009 2014 These these DT 2015 2023 findings finding NNS 2024 2033 highlight highlight VBP 2034 2037 the the DT 2038 2042 role role NN 2043 2045 of of IN 2046 2054 thrombin thrombin NN 2055 2057 as as IN 2058 2059 a a DT 2060 2069 potential potential JJ 2070 2079 regulator regulator NN 2080 2082 of of IN 2083 2084 T t NN 2085 2095 lymphocyte lymphocyte NN 2096 2106 activation activation NN 2106 2107 . . .