0 4 Cell cell NN 5 9 type type NN 10 21 specificity specificity NN 22 25 and and CC 26 36 activation activation NN 37 49 requirements requirement NNS 50 53 for for IN 54 60 NFAT-1 nfat-1 NN 61 62 ( ( ( 62 69 nuclear nuclear JJ 70 76 factor factor NN 77 79 of of IN 80 89 activated activate VBN 90 97 T-cells t-cell NNS 97 98 ) ) ) 99 114 transcriptional transcriptional JJ 115 123 activity activity NN 124 134 determined determine VBN 135 137 by by IN 138 139 a a DT 140 143 new new JJ 144 150 method method NN 151 156 using use VBG 157 167 transgenic transgenic JJ 168 172 mice mouse NNS 173 175 to to TO 176 181 assay assay VB 182 197 transcriptional transcriptional JJ 198 206 activity activity NN 207 209 of of IN 210 212 an an DT 213 223 individual individual JJ 224 231 nuclear nuclear JJ 232 238 factor factor NN 238 239 . . . 241 248 Nuclear nuclear JJ 249 255 factor factor NN 256 258 of of IN 259 268 activated activate VBN 269 276 T-cells t-cell NNS 277 278 ( ( ( 278 284 NFAT-1 nfat-1 NN 284 285 ) ) ) 286 288 is be VBZ 289 290 a a DT 291 304 transcription transcription NN 305 311 factor factor NN 312 317 which which WDT 318 320 is be VBZ 321 331 considered consider VBN 332 334 to to TO 335 337 be be VB 338 340 an an DT 341 350 important important JJ 351 360 regulator regulator NN 361 363 in in IN 364 369 early early JJ 370 376 T-cell t-cell NN 377 387 activation activation NN 387 388 . . . 389 391 We we PRP 392 396 have have VBP 397 406 developed develop VBN 407 408 a a DT 409 415 system system NN 416 418 to to TO 419 426 monitor monitor VB 427 430 the the DT 431 446 transcriptional transcriptional JJ 447 455 activity activity NN 456 458 of of IN 459 465 NFAT-1 nfat-1 NN 466 468 at at IN 469 472 the the DT 473 479 single single JJ 480 484 cell cell NN 485 490 level level NN 491 493 in in IN 494 499 whole whole JJ 500 507 animals animal NNS 507 508 . . . 509 512 The the DT 513 519 system system NN 520 522 is be VBZ 523 528 based base VBN 529 531 on on IN 532 535 the the DT 536 539 use use NN 540 542 of of IN 543 545 an an DT 546 558 oligomerized oligomerized JJ 559 565 NFAT-1 nfat-1 NN 566 573 binding binding NN 574 579 motif motif NN 580 584 that that WDT 585 592 directs direct VBZ 593 606 transcription transcription NN 607 609 of of IN 610 614 SV40 sv40 NN 615 624 T-antigen t-antigen NN 625 627 in in IN 628 638 transgenic transgenic JJ 639 643 mice mouse NNS 643 644 . . . 645 649 This this DT 650 656 report report NN 657 667 represents represent VBZ 668 671 the the DT 672 677 first first JJ 678 691 demonstration demonstration NN 692 696 that that IN 697 698 a a DT 699 711 multimerized multimerized JJ 712 717 short short JJ 718 725 binding binding NN 726 731 motif motif NN 732 735 can can MD 736 744 function function VB 745 758 appropriately appropriately RB 759 761 in in IN 762 772 transgenic transgenic JJ 773 777 mice mouse NNS 777 778 . . . 779 785 NFAT-1 nfat-1 NN 786 794 activity activity NN 795 798 had have VBD 799 809 previously previously RB 810 814 been be VBN 815 822 thought think VBN 823 825 to to TO 826 828 be be VB 829 837 confined confine VBN 838 840 to to TO 841 850 activated activate VBN 851 864 T-lymphocytes t-lymphocyte NNS 865 869 upon upon IN 870 877 release release NN 878 880 of of IN 881 894 intracellular intracellular JJ 895 902 calcium calcium NN 902 903 . . . 904 906 By by IN 907 916 targeting target VBG 917 933 NFAT-1-dependent nfat-1-dependent JJ 934 938 gene gene NN 939 949 expression expression NN 950 952 in in IN 953 963 transgenic transgenic JJ 964 968 mice mouse NNS 969 971 we we PRP 972 982 discovered discover VBD 983 986 new new JJ 987 992 sites site NNS 993 995 of of IN 996 1002 NFAT-1 nfat-1 NN 1003 1011 activity activity NN 1011 1012 . . . 1013 1020 Besides besides IN 1021 1023 in in IN 1024 1037 T-lymphocytes T-lymphocyte NNP 1038 1044 NFAT-1 nfat-1 NN 1045 1053 activity activity NN 1054 1059 could could MD 1060 1064 also also RB 1065 1067 be be VB 1068 1075 induced induce VBN 1076 1078 in in IN 1079 1100 T-lymphocyte-depleted t-lymphocyte-depleted JJ 1101 1107 spleen spleen NN 1108 1113 cells cell NNS 1114 1117 and and CC 1118 1126 purified purify VBN 1127 1140 B-lymphocytes b-lymphocyte NNS 1141 1144 and and CC 1145 1153 requires require VBZ 1154 1160 agents agent NNS 1161 1165 that that IN 1166 1170 both both CC 1171 1178 release release VB 1179 1192 intracellular intracellular JJ 1193 1200 calcium calcium NN 1201 1204 and and CC 1205 1213 activate activate VBP 1214 1221 protein protein NN 1222 1228 kinase kinase NNP 1229 1230 C C NNP 1230 1231 . . . 1232 1233 A a DT 1234 1244 difference difference NN 1245 1247 in in IN 1248 1251 the the DT 1252 1256 time time NN 1257 1263 course course NN 1264 1266 of of IN 1267 1277 appearance appearance NN 1278 1280 of of IN 1281 1287 NFAT-1 nfat-1 NN 1288 1296 activity activity NN 1297 1304 between between IN 1305 1318 T-lymphocytes t-lymphocyte NNS 1319 1322 and and CC 1323 1340 non-T-lymphocytes non-t-lymphocyte NNS 1341 1344 was be VBD 1345 1353 revealed reveal VBN 1353 1354 . . . 1355 1367 Constitutive constitutive JJ 1368 1378 expression expression NN 1379 1382 was be VBD 1383 1391 observed observe VBN 1392 1394 in in IN 1395 1396 a a DT 1397 1402 small small JJ 1403 1413 population population NN 1414 1416 of of IN 1417 1422 cells cell NNS 1423 1425 in in IN 1426 1429 the the DT 1430 1436 dermis dermis NN 1437 1440 and and CC 1441 1445 some some DT 1446 1450 mice mouse NNS 1451 1455 have have VBP 1456 1465 developed develop VBN 1466 1470 skin skin NN 1471 1478 lesions lesion NNS 1478 1479 . . . 1480 1493 Interestingly interestingly RB 1493 1494 , , , 1495 1498 the the DT 1499 1505 tissue tissue NN 1506 1513 pattern pattern NN 1514 1516 of of IN 1517 1527 expression expression NN 1528 1530 of of IN 1531 1534 the the DT 1535 1541 NFAT-1 nfat-1 NN 1542 1550 activity activity NN 1551 1560 resembles resemble VBZ 1561 1564 the the DT 1565 1575 expression expression NN 1576 1583 pattern pattern NN 1584 1593 described describe VBN 1594 1597 for for IN 1598 1609 HIV-LTR/tat HIV-LTR/tat NNP 1610 1620 transgenic transgenic JJ 1621 1625 mice mouse NNS 1626 1627 ( ( ( 1627 1632 Vogel Vogel NNP 1632 1633 , , , 1634 1636 J. J. NNP 1636 1637 , , , 1638 1646 Hinrichs Hinrichs NNP 1646 1647 , , , 1648 1650 S. S. NNP 1651 1653 H. H. NNP 1653 1654 , , , 1655 1663 Reynolds Reynolds NNP 1663 1664 , , , 1665 1667 R. R. NNP 1668 1670 K. K. NNP 1670 1671 , , , 1672 1677 Luciw Luciw NNP 1677 1678 , , , 1679 1681 P. P. NNP 1682 1684 A. A. NNP 1684 1685 , , , 1686 1689 and and CC 1690 1693 Jay Jay NNP 1693 1694 , , , 1695 1697 G. G. NNP 1698 1699 ( ( ( 1699 1703 1988 1988 CD 1703 1704 ) ) ) 1705 1711 Nature Nature NNP 1712 1715 335 335 CD 1715 1716 , , , 1717 1724 606-611 606-611 CD 1724 1725 ) ) ) 1725 1726 . . . 1727 1731 This this DT 1732 1742 similarity similarity NN 1743 1745 in in IN 1746 1756 expression expression NN 1757 1760 and and CC 1761 1764 the the DT 1765 1769 fact fact NN 1770 1774 that that IN 1775 1781 NFAT-1 NFAT-1 NNP 1782 1785 has have VBZ 1786 1790 been be VBN 1791 1796 shown show VBN 1797 1799 to to TO 1800 1804 bind bind VB 1805 1815 functional functional JJ 1816 1825 sequences sequence NNS 1826 1828 in in IN 1829 1836 HIV-LTR HIV-LTR NNP 1837 1844 suggest suggest VBP 1845 1846 a a DT 1847 1851 role role NN 1852 1855 for for IN 1856 1862 NFAT-1 nfat-1 NN 1863 1865 in in IN 1866 1872 dermal dermal JJ 1873 1883 activation activation NN 1884 1886 of of IN 1887 1890 the the DT 1891 1898 HIV-LTR hiv-ltr NN 1898 1899 . . .