0 1 A a DT 2 12 functional functional JJ 13 19 T-cell t-cell NN 20 28 receptor receptor NN 29 38 signaling signaling NN 39 46 pathway pathway NN 47 49 is be VBZ 50 58 required require VBN 59 62 for for IN 63 69 p95vav p95vav NN 70 78 activity activity NN 78 79 . . . 81 92 Stimulation stimulation NN 93 95 of of IN 96 99 the the DT 100 106 T-cell t-cell NN 107 114 antigen antigen NN 115 123 receptor receptor NN 124 125 ( ( ( 125 128 TCR TCR NNP 128 129 ) ) ) 130 137 induces induce VBZ 138 148 activation activation NN 149 151 of of IN 152 160 multiple multiple JJ 161 169 tyrosine tyrosine NN 170 177 kinases kinase NNS 177 178 , , , 179 188 resulting result VBG 189 191 in in IN 192 207 phosphorylation phosphorylation NN 208 210 of of IN 211 219 numerous numerous JJ 220 233 intracellular intracellular JJ 234 244 substrates substrate NNS 244 245 . . . 246 249 One one CD 250 259 substrate substrate NN 260 262 is be VBZ 263 269 p95vav p95vav NN 269 270 , , , 271 276 which which WDT 277 279 is be VBZ 280 289 expressed express VBN 290 301 exclusively exclusively RB 302 304 in in IN 305 318 hematopoietic hematopoietic JJ 319 322 and and CC 323 334 trophoblast trophoblast NN 335 340 cells cell NNS 340 341 . . . 342 344 It it PRP 345 353 contains contain VBZ 354 355 a a DT 356 362 number number NN 363 365 of of IN 366 376 structural structural JJ 377 383 motifs motif NNS 383 384 , , , 385 394 including include VBG 395 398 Src Src NNP 399 407 homology homology NN 408 409 2 2 CD 409 410 , , , 411 414 Src Src NNP 415 423 homology homology NN 424 425 3 3 CD 425 426 , , , 427 430 and and CC 431 441 pleckstrin pleckstrin NN 442 450 homology homology NN 451 458 domains domain NNS 459 462 and and CC 463 464 a a DT 465 473 putative putative JJ 474 481 guanine guanine NN 482 492 nucleotide nucleotide NN 493 501 exchange exchange NN 502 508 domain domain NN 508 509 . . . 510 513 The the DT 514 518 role role NN 519 521 of of IN 522 528 p95vav p95vav NN 529 531 in in IN 532 544 TCR-mediated tcr-mediated JJ 545 554 signaling signaling NN 555 564 processes process NNS 565 567 is be VBZ 568 575 unclear unclear JJ 575 576 . . . 577 581 Here here RB 581 582 , , , 583 585 we we PRP 586 590 show show VBP 591 595 that that IN 596 610 overexpression overexpression NN 611 613 of of IN 614 620 p95vav p95vav NN 621 626 alone alone RB 627 629 in in IN 630 636 Jurkat Jurkat NNP 637 638 T t NN 639 644 cells cell NNS 645 650 leads lead VBZ 651 653 to to TO 654 664 activation activation NN 665 667 of of IN 668 671 the the DT 672 679 nuclear nuclear JJ 680 687 factors factor NNS 687 688 , , , 689 698 including include VBG 699 703 NFAT NFAT NNP 703 704 , , , 705 713 involved involve VBN 714 716 in in IN 717 730 interleukin-2 interleukin-2 NN 731 741 expression expression NN 741 742 . . . 743 754 Furthermore furthermore RB 754 755 , , , 756 762 p95vav p95vav NN 763 773 synergizes synergize VBZ 774 778 with with IN 779 782 TCR TCR NNP 783 794 stimulation stimulation NN 795 797 in in IN 798 806 inducing induce VBG 807 812 NFAT- nfat- NN 813 816 and and CC 817 840 interleukin-2-dependent interleukin-2-dependent JJ 841 854 transcription transcription NN 854 855 . . . 856 858 In in IN 859 867 contrast contrast NN 867 868 , , , 869 873 NFAT NFAT NNP 874 884 activation activation NN 885 887 by by IN 888 889 a a DT 890 907 G-protein-coupled g-protein-coupled JJ 908 916 receptor receptor NN 917 919 is be VBZ 920 923 not not RB 924 933 modulated modulate VBN 934 936 by by IN 937 943 p95vav p95vav NN 944 958 overexpression overexpression NN 958 959 , , , 960 970 suggesting suggest VBG 971 975 that that IN 976 979 the the DT 980 986 effect effect NN 987 989 is be VBZ 990 998 specific specific JJ 999 1001 to to TO 1002 1005 the the DT 1006 1009 TCR TCR NNP 1010 1019 signaling signaling NN 1020 1028 pathways pathway NNS 1028 1029 . . . 1030 1038 Although although IN 1039 1046 removal removal NN 1047 1049 of of IN 1050 1053 the the DT 1054 1059 first first JJ 1060 1062 67 67 CD 1063 1068 amino amino NN 1069 1074 acids acid NNS 1075 1077 of of IN 1078 1084 p95vav p95vav NNP 1085 1094 activates activate VBZ 1095 1098 its its PRP$ 1099 1111 transforming transforming NN 1112 1121 potential potential NN 1122 1124 in in IN 1125 1128 NIH NIH NNP 1129 1132 3T3 3t3 NN 1133 1138 cells cell NNS 1138 1139 , , , 1140 1144 this this DT 1145 1151 region region NN 1152 1159 appears appear VBZ 1160 1162 to to TO 1163 1165 be be VB 1166 1174 required require VBN 1175 1178 for for IN 1179 1182 its its PRP$ 1183 1191 function function NN 1192 1194 in in IN 1195 1196 T t NN 1197 1202 cells cell NNS 1202 1203 . . . 1204 1206 We we PRP 1207 1214 further further RB 1215 1226 demonstrate demonstrate VBP 1227 1231 that that IN 1232 1235 the the DT 1236 1250 p95vav-induced p95vav-induced JJ 1251 1255 NFAT nfat NN 1256 1266 activation activation NN 1267 1269 is be VBZ 1270 1273 not not RB 1274 1282 mimicked mimic VBN 1283 1285 by by IN 1286 1289 Ras Ras NNP 1290 1300 activation activation NN 1300 1301 , , , 1302 1308 though though IN 1309 1312 its its PRP$ 1313 1321 function function NN 1322 1324 is be VBZ 1325 1334 dependent dependent JJ 1335 1339 upon upon IN 1340 1343 Ras Ras NNP 1344 1347 and and CC 1348 1351 Raf Raf NNP 1351 1352 . . . 1353 1364 Furthermore furthermore RB 1364 1365 , , , 1366 1369 the the DT 1370 1380 activating activate VBG 1381 1389 function function NN 1390 1392 of of IN 1393 1399 p95vav p95vav NNP 1400 1402 is be VBZ 1403 1410 blocked block VBN 1411 1413 by by IN 1414 1419 FK506 FK506 NNP 1419 1420 , , , 1421 1431 suggesting suggest VBG 1432 1436 that that IN 1437 1440 its its PRP$ 1441 1449 activity activity NN 1450 1454 also also RB 1455 1462 depends depend VBZ 1463 1465 on on IN 1466 1477 calcineurin calcineurin NN 1477 1478 . . . 1479 1481 To to TO 1482 1489 further further RBR 1490 1497 dissect dissect VB 1498 1504 p95vav p95vav NN 1505 1516 involvement involvement NN 1517 1519 in in IN 1520 1523 TCR TCR NNP 1524 1533 signaling signaling NN 1533 1534 , , , 1535 1537 we we PRP 1538 1546 analyzed analyze VBD 1547 1554 various various JJ 1555 1561 Jurkat Jurkat NNP 1562 1569 mutants mutant NNS 1570 1579 deficient deficient JJ 1580 1582 in in IN 1583 1586 TCR TCR NNP 1587 1596 signaling signaling NN 1597 1605 function function NN 1606 1608 or or CC 1609 1612 TCR TCR NNP 1613 1623 expression expression NN 1624 1627 and and CC 1628 1634 showed show VBD 1635 1639 that that IN 1640 1642 an an DT 1643 1649 intact intact JJ 1650 1653 TCR TCR NNP 1654 1663 signaling signaling NN 1664 1671 pathway pathway NN 1672 1674 is be VBZ 1675 1683 required require VBN 1684 1687 for for IN 1688 1694 p95vav p95vav NN 1695 1697 to to TO 1698 1706 function function VB 1706 1707 . . . 1708 1715 However however RB 1715 1716 , , , 1717 1731 overexpression overexpression NN 1732 1734 of of IN 1735 1741 p95vav p95vav NNP 1742 1746 does do VBZ 1747 1750 not not RB 1751 1757 appear appear VB 1758 1760 to to TO 1761 1770 influence influence VB 1771 1782 TCR-induced tcr-induced JJ 1783 1790 protein protein NN 1791 1799 tyrosine tyrosine NN 1800 1815 phosphorylation phosphorylation NN 1816 1818 or or CC 1819 1828 increases increase NNS 1829 1831 in in IN 1832 1843 cytoplasmic cytoplasmic JJ 1844 1848 free free JJ 1849 1856 calcium calcium NN 1856 1857 . . . 1858 1863 Taken take VBN 1864 1872 together together RB 1872 1873 , , , 1874 1877 our our PRP$ 1878 1882 data datum NNS 1883 1890 suggest suggest VBP 1891 1895 that that IN 1896 1902 p95vav p95vav NN 1903 1908 plays play VBZ 1909 1911 an an DT 1912 1921 important important JJ 1922 1926 role role NN 1927 1929 at at IN 1930 1932 an an DT 1933 1936 yet yet RB 1937 1949 unidentified unidentified JJ 1950 1958 proximal proximal JJ 1959 1967 position position NN 1968 1970 in in IN 1971 1974 the the DT 1975 1978 TCR TCR NNP 1979 1988 signaling signaling NN 1989 1996 cascade cascade NN 1996 1997 . . .