0 3 Itk Itk NNP 3 4 , , , 5 6 a a DT 7 8 T t NN 9 22 cell-specific cell-specific JJ 23 31 tyrosine tyrosine NN 32 38 kinase kinase NNP 38 39 , , , 40 42 is be VBZ 43 51 required require VBN 52 55 for for IN 56 68 CD2-mediated cd2-mediated JJ 69 82 interleukin-2 interleukin-2 NN 83 91 promoter promoter NN 92 102 activation activation NN 103 105 in in IN 106 109 the the DT 110 115 human human JJ 116 117 T t NN 118 122 cell cell NN 123 127 line line NN 128 134 Jurkat Jurkat NNP 134 135 . . . 137 139 We we PRP 140 152 investigated investigate VBD 153 156 the the DT 157 167 functional functional JJ 168 172 role role NN 173 175 of of IN 176 179 Itk Itk NNP 179 180 , , , 181 182 a a DT 183 189 member member NN 190 192 of of IN 193 196 the the DT 197 208 cytoplasmic cytoplasmic JJ 209 217 tyrosine tyrosine NN 218 224 kinase kinase NNP 225 228 Tec Tec NNP 229 235 family family NN 235 236 , , , 237 239 in in IN 240 241 T t NN 242 246 cell cell NN 247 257 activation activation NN 257 258 . . . 259 270 Stimulation stimulation NN 271 273 of of IN 274 280 either either CC 281 284 CD2 cd2 NN 285 287 or or CC 288 289 T t NN 290 294 cell cell NN 295 303 receptor receptor NN 304 305 ( ( ( 305 313 TCR)/CD3 TCR)/CD3 NNP 314 316 on on IN 317 323 Tcells tcell NNS 324 326 by by IN 327 337 monoclonal monoclonal JJ 338 355 antibody-mediated antibody-mediated JJ 356 369 cross-linking cross-linking NN 370 377 induced induce VBD 378 386 tyrosine tyrosine NN 387 402 phosphorylation phosphorylation NN 403 405 of of IN 406 409 Itk Itk NNP 409 410 , , , 411 416 which which WDT 417 420 was be VBD 421 428 maximal maximal JJ 429 431 as as RB 432 437 early early RB 438 440 as as IN 441 442 1 1 CD 443 446 min min NN 447 452 after after IN 453 464 stimulation stimulation NN 464 465 . . . 466 469 The the DT 470 478 tyrosine tyrosine NN 479 485 kinase kinase NNP 486 494 activity activity NN 495 497 in in IN 498 501 the the DT 502 510 anti-Itk anti-itk JJ 511 528 immunoprecipitate immunoprecipitate NN 529 532 was be VBD 533 546 significantly significantly RB 547 556 activated activate VBN 557 561 upon upon IN 562 567 these these DT 568 580 stimulations stimulation NNS 580 581 . . . 582 595 Interleukin-2 interleukin-2 NN 596 597 ( ( ( 597 601 IL-2 il-2 NN 601 602 ) ) ) 603 611 promoter promoter NN 612 620 activity activity NN 621 631 stimulated stimulate VBN 632 634 by by IN 635 648 cross-linking cross-linking NN 649 651 of of IN 652 655 CD2 cd2 NN 655 656 , , , 657 664 TCR/CD3 TCR/CD3 NNP 664 665 , , , 666 669 and and CC 670 674 CD28 cd28 NN 675 679 with with IN 680 690 antibodies antibody NNS 691 694 was be VBD 695 708 significantly significantly RB 709 716 reduced reduce VBN 717 719 by by IN 720 729 transient transient JJ 730 740 expression expression NN 741 743 of of IN 744 746 an an DT 747 750 Itk Itk NNP 751 757 mutant mutant NN 758 765 lacking lack VBG 766 769 the the DT 770 776 kinase kinase NNP 777 785 activity activity NN 785 786 . . . 787 790 The the DT 791 800 reduction reduction NN 801 811 paralleled parallel VBD 812 813 a a DT 814 822 decrease decrease NN 823 825 in in IN 826 834 tyrosine tyrosine NN 835 850 phosphorylation phosphorylation NN 851 853 of of IN 854 864 endogenous endogenous JJ 865 874 wild-type wild-type JJ 875 878 Itk itk NN 878 879 . . . 880 891 Stimulation stimulation NN 892 894 of of IN 895 898 CD2 cd2 NN 899 901 or or CC 902 909 TCR/CD3 TCR/CD3 NNP 910 917 induced induce VBD 918 928 activation activation NN 929 931 of of IN 932 935 the the DT 936 943 nuclear nuclear JJ 944 950 factor factor NN 951 953 of of IN 954 963 activated activate VBN 964 965 T t NN 966 971 cells cell NNS 972 973 ( ( ( 973 977 NFAT NFAT NNP 977 978 ) ) ) 978 979 , , , 980 983 the the DT 984 991 binding bind VBG 992 996 site site NN 997 999 of of IN 1000 1005 which which WDT 1006 1008 is be VBZ 1009 1017 included include VBN 1018 1020 in in IN 1021 1024 the the DT 1025 1029 IL-2 il-2 NN 1030 1034 gene gene NN 1035 1043 promoter promoter NN 1043 1044 . . . 1045 1048 The the DT 1049 1059 activation activation NN 1060 1062 of of IN 1063 1067 NFAT NFAT NNP 1068 1071 was be VBD 1072 1076 also also RB 1077 1085 impaired impair VBN 1086 1088 by by IN 1089 1099 expression expression NN 1100 1102 of of IN 1103 1106 the the DT 1107 1110 Itk Itk NNP 1111 1117 mutant mutant NN 1117 1118 . . . 1119 1124 These these DT 1125 1132 results result NNS 1133 1144 demonstrate demonstrate VBP 1145 1149 that that IN 1150 1153 Itk Itk NNP 1154 1159 plays play VBZ 1160 1161 a a DT 1162 1166 role role NN 1167 1169 in in IN 1170 1174 IL-2 il-2 NN 1175 1185 production production NN 1185 1186 , , , 1187 1197 indicating indicate VBG 1198 1199 a a DT 1200 1208 critical critical JJ 1209 1220 involvement involvement NN 1221 1223 of of IN 1224 1227 Itk Itk NNP 1228 1230 in in IN 1231 1234 the the DT 1235 1242 initial initial JJ 1243 1248 stage stage NN 1249 1251 of of IN 1252 1253 T t NN 1254 1258 cell cell NN 1259 1269 activation activation NN 1270 1272 by by IN 1273 1282 mediating mediate VBG 1283 1290 signals signal NNS 1291 1295 from from IN 1296 1299 the the DT 1300 1307 TCR/CD3 tcr/cd3 NN 1308 1315 complex complex NN 1315 1316 , , , 1317 1320 CD2 cd2 NN 1320 1321 , , , 1322 1325 and and CC 1326 1330 CD28 cd28 NN 1330 1331 . . .