0 9 Induction Induction NNP 10 12 of of IN 13 21 tyrosine tyrosine NN 22 37 phosphorylation phosphorylation NN 38 41 and and CC 42 48 T-cell t-cell NN 49 59 activation activation NN 60 62 by by IN 63 71 vanadate vanadate NN 72 80 peroxide peroxide NN 80 81 , , , 82 84 an an DT 85 94 inhibitor inhibitor NN 95 97 of of IN 98 105 protein protein NN 106 114 tyrosine tyrosine NN 115 127 phosphatases phosphatas NNS 127 128 . . . 130 135 Rapid rapid JJ 136 144 tyrosine tyrosine NN 145 160 phosphorylation phosphorylation NN 161 163 of of IN 164 167 key key JJ 168 176 cellular cellular JJ 177 185 proteins protein NNS 186 188 is be VBZ 189 190 a a DT 191 198 crucial crucial JJ 199 204 event event NN 205 207 in in IN 208 211 the the DT 212 224 transduction transduction NN 225 227 of of IN 228 238 activation activation NN 239 246 signals signal NNS 247 249 to to TO 250 263 T-lymphocytes t-lymphocyte NNS 263 264 . . . 265 268 The the DT 269 279 regulatory regulatory JJ 280 284 role role NN 285 287 of of IN 288 295 protein protein NN 296 304 tyrosine tyrosine NN 305 317 phosphatases phosphatas NNS 318 319 ( ( ( 319 326 PTPases ptpas NNS 326 327 ) ) ) 328 330 in in IN 331 335 this this DT 336 343 process process NN 344 347 was be VBD 348 356 explored explore VBN 357 359 by by IN 360 368 studying study VBG 369 372 the the DT 373 380 effects effect NNS 381 383 of of IN 384 385 a a DT 386 394 powerful powerful JJ 395 401 PTPase ptpase NN 402 411 inhibitor inhibitor NN 411 412 , , , 413 421 vanadate vanadate NN 422 430 peroxide peroxide NN 431 432 ( ( ( 432 443 pervanadate pervanadate NN 443 444 ) ) ) 444 445 , , , 446 448 on on IN 449 452 the the DT 453 463 activation activation NN 464 471 cascade cascade NN 472 474 of of IN 475 481 Jurkat Jurkat NNP 482 487 human human JJ 488 497 leukaemic leukaemic JJ 498 505 T-cells t-cell NNS 505 506 . . . 507 518 Pervanadate Pervanadate NNP 519 526 induced induce VBD 527 537 activation activation NN 538 540 of of IN 541 544 the the DT 545 553 tyrosine tyrosine NN 554 561 kinases kinase NNS 562 565 lck lck NN 566 569 and and CC 570 573 fyn fyn NN 574 575 ( ( ( 575 577 4- 4- CD 578 581 and and CC 582 588 3-fold 3-fold RB 589 601 respectively respectively RB 601 602 ) ) ) 603 606 and and CC 607 608 a a DT 609 617 dramatic dramatic JJ 618 626 increase increase NN 627 629 in in IN 630 638 tyrosine tyrosine NN 639 654 phosphorylation phosphorylation NN 655 657 of of IN 658 666 cellular cellular JJ 667 675 proteins protein NNS 675 676 , , , 677 684 notably notably RB 685 698 phospholipase phospholipase NN 699 700 C C NNP 701 706 gamma gamma NN 707 708 1 1 CD 708 709 . . . 710 715 After after IN 716 720 this this DT 721 726 event event NN 726 727 , , , 728 730 we we PRP 731 739 observed observe VBD 740 741 a a DT 742 746 rise rise NN 747 749 in in IN 750 763 intracellular intracellular JJ 764 768 Ca2+ ca2+ NN 769 782 concentration concentration NN 782 783 , , , 784 797 corresponding correspond VBG 798 800 to to TO 801 803 an an DT 804 810 influx influx NN 810 811 . . . 812 816 This this DT 817 823 effect effect NN 824 832 required require VBD 833 840 surface surface NN 841 851 expression expression NN 852 854 of of IN 855 858 the the DT 859 863 CD45 CD45 NNP 864 870 PTPase PTPase NNP 871 874 and and CC 875 878 was be VBD 879 882 not not RB 883 891 observed observe VBN 892 894 in in IN 895 909 CD45-deficient cd45-deficient JJ 910 918 variants variant NNS 919 921 of of IN 922 928 Jurkat Jurkat NNP 929 934 cells cell NNS 934 935 . . . 936 938 In in IN 939 942 the the DT 943 956 CD45-negative cd45-negative JJ 957 964 variant variant NN 964 965 , , , 966 969 the the DT 970 976 effect effect NN 977 979 of of IN 980 991 pervanadate pervanadate NN 992 994 on on IN 995 1003 tyrosine tyrosine NN 1004 1019 phosphorylation phosphorylation NN 1020 1023 was be VBD 1024 1032 globally globally RB 1033 1042 decreased decrease VBN 1043 1046 and and CC 1047 1051 some some DT 1052 1066 phosphorylated phosphorylate VBN 1067 1077 substrates substrate NNS 1078 1082 were be VBD 1083 1095 specifically specifically RB 1096 1103 missing missing JJ 1103 1104 . . . 1105 1116 Pervanadate Pervanadate NNP 1117 1121 also also RB 1122 1132 stimulated stimulate VBD 1133 1146 transcription transcription NN 1147 1149 of of IN 1150 1153 the the DT 1154 1159 c-fos c-fos NN 1160 1164 gene gene NN 1165 1168 and and CC 1169 1181 accumulation accumulation NN 1182 1184 of of IN 1185 1188 its its PRP$ 1189 1193 mRNA mrna NN 1194 1196 as as RB 1197 1201 well well RB 1202 1204 as as IN 1205 1212 several several JJ 1213 1218 other other JJ 1219 1228 hallmarks hallmark NNS 1229 1231 of of IN 1232 1244 T-lymphocyte T-lymphocyte NNP 1245 1255 activation activation NN 1256 1260 such such JJ 1261 1263 as as IN 1264 1271 surface surface NN 1272 1282 expression expression NN 1283 1285 of of IN 1286 1289 the the DT 1290 1294 CD69 CD69 NNP 1295 1302 antigen antigen NN 1303 1306 and and CC 1307 1310 the the DT 1311 1322 interleukin interleukin NN 1323 1324 2 2 CD 1325 1333 receptor receptor NN 1334 1345 alpha-chain alpha-chain NN 1346 1347 ( ( ( 1347 1351 CD25 cd25 NN 1351 1352 ) ) ) 1352 1353 . . . 1354 1365 Pervanadate Pervanadate NNP 1366 1376 synergized synergize VBD 1377 1381 with with IN 1382 1389 signals signal NNS 1390 1399 delivered deliver VBN 1400 1402 by by IN 1403 1409 T-cell t-cell NN 1410 1417 antigen antigen NN 1418 1426 receptor receptor NN 1427 1437 engagement engagement NN 1438 1440 or or CC 1441 1443 by by IN 1444 1445 a a DT 1446 1453 phorbol phorbol NN 1454 1459 ester ester NN 1460 1462 to to TO 1463 1469 induce induce VB 1470 1481 interleukin interleukin NN 1482 1483 2 2 CD 1484 1494 production production NN 1494 1495 . . . 1496 1507 Pervanadate Pervanadate NNP 1508 1517 activated activate VBD 1518 1526 NF-kappa NF-kappa NNP 1527 1528 B B NNP 1528 1529 , , , 1530 1532 as as IN 1533 1538 shown show VBN 1539 1541 by by IN 1542 1544 an an DT 1545 1553 increase increase NN 1554 1556 in in IN 1557 1568 DNA-binding dna-binding JJ 1569 1577 activity activity NN 1578 1580 of of IN 1581 1585 this this DT 1586 1599 transcription transcription NN 1600 1606 factor factor NN 1606 1607 . . . 1608 1610 We we PRP 1611 1615 thus thus RB 1616 1624 conclude conclude VBP 1625 1629 that that IN 1630 1637 PTPases ptpas NNS 1638 1642 play play VBP 1643 1644 a a DT 1645 1652 crucial crucial JJ 1653 1657 role role NN 1658 1660 in in IN 1661 1664 the the DT 1665 1673 negative negative JJ 1674 1684 regulation regulation NN 1685 1687 of of IN 1688 1694 signal signal NN 1695 1707 transduction transduction NN 1708 1719 culminating culminate VBG 1720 1722 in in IN 1723 1735 T-lymphocyte T-lymphocyte NNP 1736 1746 activation activation NN 1746 1747 . . . 1748 1756 Moreover moreover RB 1756 1757 , , , 1758 1767 induction induction NN 1768 1770 of of IN 1771 1779 tyrosine tyrosine NN 1780 1795 phosphorylation phosphorylation NN 1796 1803 appears appear VBZ 1804 1814 sufficient sufficient JJ 1815 1818 per per FW 1819 1821 se se FW 1822 1824 to to TO 1825 1833 initiate initiate VB 1834 1835 a a DT 1836 1844 complete complete JJ 1845 1855 activation activation NN 1856 1865 programme programme NN 1865 1866 . . .