0 10 Inhibition Inhibition NNP 11 13 of of IN 14 15 T t NN 16 20 cell cell NN 21 30 signaling signaling NN 31 33 by by IN 34 51 mitogen-activated mitogen-activated JJ 52 59 protein protein NN 60 75 kinase-targeted kinase-targeted JJ 76 89 hematopoietic hematopoietic JJ 90 98 tyrosine tyrosine NN 99 110 phosphatase phosphatase NN 111 112 ( ( ( 112 117 HePTP HePTP NNP 117 118 ) ) ) 118 119 . . . 121 131 Activation Activation NNP 132 134 of of IN 135 136 T t NN 137 148 lymphocytes lymphocyte NNS 149 151 to to TO 152 159 produce produce VB 160 169 cytokines cytokine NNS 170 172 is be VBZ 173 182 regulated regulate VBN 183 185 by by IN 186 189 the the DT 190 204 counterbalance counterbalance NN 205 207 of of IN 208 224 protein-tyrosine protein-tyrosine JJ 225 232 kinases kinase NNS 233 236 and and CC 237 253 protein-tyrosine protein-tyrosine JJ 254 266 phosphatases phosphatas NNS 266 267 , , , 268 272 many many JJ 273 275 of of IN 276 281 which which WDT 282 286 have have VBP 287 288 a a DT 289 293 high high JJ 294 300 degree degree NN 301 303 of of IN 304 313 substrate substrate NN 314 325 specificity specificity NN 326 333 because because IN 334 336 of of IN 337 345 physical physical JJ 346 357 association association NN 358 362 with with IN 363 368 their their PRP$ 369 376 targets target NNS 376 377 . . . 378 392 Overexpression overexpression NN 393 395 of of IN 396 409 hematopoietic hematopoietic JJ 410 426 protein-tyrosine protein-tyrosine JJ 427 438 phosphatase phosphatase NN 439 440 ( ( ( 440 445 HePTP HePTP NNP 445 446 ) ) ) 447 454 results result VBZ 455 457 in in IN 458 469 suppression suppression NN 470 472 of of IN 473 474 T t NN 475 485 lymphocyte lymphocyte NN 486 496 activation activation NN 497 499 as as IN 500 508 measured measure VBN 509 511 by by IN 512 513 T t NN 514 518 cell cell NN 519 526 antigen antigen NN 527 543 receptor-induced receptor-induced JJ 544 554 activation activation NN 555 557 of of IN 558 571 transcription transcription NN 572 579 factors factor NNS 580 587 binding bind VBG 588 590 to to TO 591 594 the the DT 595 596 5 5 CD 596 597 ’ ' SYM 598 606 promoter promoter NN 607 609 of of IN 610 613 the the DT 614 627 interleukin-2 interleukin-2 NN 628 632 gene gene NN 632 633 . . . 634 641 Efforts effort NNS 642 644 to to TO 645 653 pinpoint pinpoint VB 654 657 the the DT 658 663 exact exact JJ 664 668 site site NN 669 671 of of IN 672 678 action action NN 679 682 and and CC 683 694 specificity specificity NN 695 697 of of IN 698 703 HePTP HePTP NNP 704 706 in in IN 707 710 the the DT 711 720 signaling signaling NN 721 728 cascade cascade NN 729 737 revealed reveal VBD 738 742 that that IN 743 748 HePTP HePTP NNP 749 753 acts act VBZ 754 762 directly directly RB 763 765 on on IN 766 769 the the DT 770 787 mitogen-activated mitogen-activated JJ 788 795 protein protein NN 796 797 ( ( ( 797 800 MAP MAP NNP 800 801 ) ) ) 802 809 kinases kinase NNS 810 814 Erk1 erk1 NN 815 818 and and CC 819 820 2 2 CD 821 824 and and CC 825 837 consequently consequently RB 838 845 reduces reduce VBZ 846 849 the the DT 850 859 magnitude magnitude NN 860 863 and and CC 864 872 duration duration NN 873 875 of of IN 876 881 their their PRP$ 882 891 catalytic catalytic JJ 892 902 activation activation NN 903 905 in in IN 906 912 intact intact JJ 913 914 T t NN 915 920 cells cell NNS 920 921 . . . 922 924 In in IN 925 933 contrast contrast NN 933 934 , , , 935 940 HePTP HePTP NNP 941 944 had have VBD 945 947 no no DT 948 955 effects effect NNS 956 958 on on IN 959 969 N-terminal n-terminal JJ 970 975 c-Jun c-jun NN 976 982 kinase kinase NNP 983 985 or or CC 986 988 on on IN 989 995 events event NNS 996 1004 upstream upstream RB 1005 1007 of of IN 1008 1011 the the DT 1012 1015 MAP MAP NNP 1016 1023 kinases kinase NNS 1023 1024 . . . 1025 1028 The the DT 1029 1040 specificity specificity NN 1041 1043 of of IN 1044 1049 HePTP HePTP NNP 1050 1060 correlated correlate VBD 1061 1065 with with IN 1066 1069 its its PRP$ 1070 1078 physical physical JJ 1079 1090 association association NN 1091 1098 through through IN 1099 1102 its its PRP$ 1103 1115 noncatalytic noncatalytic JJ 1116 1117 N N NNP 1118 1126 terminus terminus NN 1127 1131 with with IN 1132 1135 Erk Erk NNP 1136 1139 and and CC 1140 1147 another another DT 1148 1151 MAP MAP NNP 1152 1158 kinase kinase NNP 1158 1159 , , , 1160 1163 p38 p38 NN 1163 1164 , , , 1165 1168 but but CC 1169 1172 not not RB 1173 1176 Jnk Jnk NNP 1177 1179 or or CC 1180 1185 other other JJ 1186 1194 proteins protein NNS 1194 1195 . . . 1196 1198 We we PRP 1199 1206 propose propose VBP 1207 1211 that that IN 1212 1217 HePTP HePTP NNP 1218 1223 plays play VBZ 1224 1225 a a DT 1226 1234 negative negative JJ 1235 1239 role role NN 1240 1242 in in IN 1243 1250 antigen antigen NN 1251 1259 receptor receptor NN 1260 1269 signaling signaling NN 1270 1272 by by IN 1273 1285 specifically specifically RB 1286 1296 regulating regulate VBG 1297 1300 MAP MAP NNP 1301 1308 kinases kinase NNS 1309 1311 in in IN 1312 1315 the the DT 1316 1323 cytosol cytosol NN 1324 1327 and and CC 1328 1330 at at IN 1331 1336 early early JJ 1337 1341 time time NN 1342 1348 points point NNS 1349 1351 of of IN 1352 1353 T t NN 1354 1358 cell cell NN 1359 1369 activation activation NN 1370 1376 before before IN 1377 1380 the the DT 1381 1399 activation-induced activation-induced JJ 1400 1410 expression expression NN 1411 1413 of of IN 1414 1421 nuclear nuclear JJ 1422 1435 dual-specific dual-specific JJ 1436 1439 MAP MAP NNP 1440 1446 kinase kinase NNP 1447 1459 phosphatases phosphatas NNS 1459 1460 . . .