0 10 Activation Activation NNP 11 14 and and CC 15 25 expression expression NN 26 28 of of IN 29 32 the the DT 33 40 nuclear nuclear JJ 41 48 factors factor NNS 49 51 of of IN 52 61 activated activate VBN 62 63 T t NN 64 69 cells cell NNS 69 70 , , , 71 76 NFATp NFATp NNP 77 80 and and CC 81 86 NFATc NFATc NNP 86 87 , , , 88 90 in in IN 91 96 human human JJ 97 104 natural natural JJ 105 111 killer killer NN 112 117 cells cell NNS 117 118 : : : 119 129 regulation regulation NN 130 134 upon upon IN 135 139 CD16 CD16 NNP 140 146 ligand ligand NN 147 154 binding binding NN 154 155 . . . 157 160 The the DT 161 169 putative putative JJ 170 177 factors factor NNS 178 182 that that WDT 183 189 couple couple VBP 190 193 the the DT 194 200 signal signal NN 201 213 transduction transduction NN 214 218 from from IN 219 226 surface surface NN 227 236 receptors receptor NNS 237 239 to to TO 240 243 the the DT 244 254 activation activation NN 255 257 of of IN 258 266 cytokine cytokine NN 267 276 synthesis synthesis NN 277 279 in in IN 280 287 natural natural JJ 288 294 killer killer NN 295 296 ( ( ( 296 298 NK NK NNP 298 299 ) ) ) 300 305 cells cell NNS 306 310 have have VBP 311 314 not not RB 315 319 been be VBN 320 330 elucidated elucidate VBN 330 331 . . . 332 334 We we PRP 335 341 report report VBP 342 346 here here RB 347 351 that that IN 352 355 the the DT 356 363 nuclear nuclear JJ 364 370 factor factor NN 371 373 of of IN 374 383 activated activate VBN 384 385 T t NN 386 391 cells cell NNS 392 393 ( ( ( 393 398 NFATp NFATp NNP 398 399 ) ) ) 399 400 , , , 401 402 a a DT 403 414 cyclosporin cyclosporin NN 415 416 A a NN 417 418 ( ( ( 418 432 CsA)-sensitive csa)-sensitive JJ 433 439 factor factor NN 440 444 that that WDT 445 454 regulates regulate VBZ 455 458 the the DT 459 472 transcription transcription NN 473 475 of of IN 476 483 several several JJ 484 493 cytokines cytokine NNS 493 494 , , , 495 503 mediates mediate VBZ 504 516 CD16-induced cd16-induced JJ 517 527 activation activation NN 528 530 of of IN 531 539 cytokine cytokine NN 540 545 genes gene NNS 546 548 in in IN 549 554 human human JJ 555 557 NK nk NN 558 563 cells cell NNS 563 564 . . . 565 569 CD16 CD16 NNP 570 571 ( ( ( 571 573 Fc Fc NNP 574 579 gamma gamma NN 580 594 RIIIA)-induced riiia)-induced JJ 595 605 expression expression NN 606 608 of of IN 609 617 cytokine cytokine NN 618 622 mRNA mrna NN 623 625 in in IN 626 628 NK NK NNP 629 634 cells cell NNS 635 641 occurs occur VBZ 642 645 via via IN 646 647 a a DT 648 661 CsA-sensitive csa-sensitive JJ 662 665 and and CC 666 682 Ca(2+)-dependent ca(2+)-dependent JJ 683 692 mechanism mechanism NN 692 693 . . . 694 705 Stimulation stimulation NN 706 708 of of IN 709 711 NK NK NNP 712 717 cells cell NNS 718 722 with with IN 723 727 CD16 cd16 NN 728 735 ligands ligand NNS 736 743 induces induce VBZ 744 753 NFAT-like nfat-like JJ 754 757 DNA dna NN 758 765 binding binding NN 766 774 activity activity NN 775 777 in in IN 778 781 the the DT 782 789 nuclear nuclear JJ 790 798 extracts extract NNS 799 803 from from IN 804 809 these these DT 810 815 cells cell NNS 815 816 , , , 817 819 as as IN 820 828 detected detect VBN 829 831 in in IN 832 847 electrophoretic electrophoretic JJ 848 856 mobility mobility NN 857 862 shift shift NN 863 869 assays assay NNS 869 870 . . . 871 875 This this DT 876 882 occurs occur VBZ 883 887 with with IN 888 892 fast fast JJ 893 901 kinetics kinetic NNS 902 907 after after IN 908 919 stimulation stimulation NN 919 920 , , , 921 924 via via IN 925 926 a a DT 927 940 CsA-sensitive csa-sensitive JJ 941 944 and and CC 945 961 Ca(2+)-dependent ca(2+)-dependent JJ 962 971 mechanism mechanism NN 972 976 that that WDT 977 981 does do VBZ 982 985 not not RB 986 993 require require VB 994 996 de de FW 997 1001 novo novo FW 1002 1009 protein protein NN 1010 1019 synthesis synthesis NN 1019 1020 . . . 1021 1023 NK NK NNP 1024 1028 cell cell NN 1029 1033 NFAT nfat NN 1034 1036 is be VBZ 1037 1044 present present JJ 1045 1047 in in IN 1048 1051 the the DT 1052 1059 cytosol cytosol NN 1060 1062 of of IN 1063 1076 nonstimulated nonstimulated JJ 1077 1082 cells cell NNS 1082 1083 , , , 1084 1092 migrates migrate NNS 1093 1095 to to TO 1096 1099 the the DT 1100 1107 nucleus nucleus NN 1108 1112 upon upon IN 1113 1124 stimulation stimulation NN 1124 1125 , , , 1126 1129 and and CC 1130 1133 can can MD 1134 1143 associate associate VB 1144 1148 with with IN 1149 1153 AP-1 ap-1 NN 1153 1154 . . . 1155 1158 Two two CD 1159 1167 distinct distinct JJ 1168 1177 molecules molecule NNS 1177 1178 , , , 1179 1184 NFATp NFATp NNP 1185 1188 and and CC 1189 1194 NFATc NFATc NNP 1194 1195 , , , 1196 1200 have have VBP 1201 1205 been be VBN 1206 1214 reported report VBN 1215 1217 to to TO 1218 1225 mediate mediate VB 1226 1230 NFAT nfat NN 1231 1239 activity activity NN 1239 1240 . . . 1241 1244 The the DT 1245 1252 results result NNS 1253 1255 of of IN 1256 1266 supershift supershift NN 1267 1273 assays assay NNS 1274 1279 using use VBG 1280 1286 NFATp- nfatp- NN 1287 1290 and and CC 1291 1297 NFATc- nfatc- NN 1298 1306 specific specific JJ 1307 1317 antibodies antibody NNS 1318 1326 indicate indicate VBP 1327 1331 that that IN 1332 1334 NK NK NNP 1335 1339 cell cell NN 1340 1350 activation activation NN 1351 1356 early early RB 1357 1362 after after IN 1363 1367 CD16 CD16 NNP 1368 1374 ligand ligand NN 1375 1382 binding binding NN 1383 1391 involves involve VBZ 1392 1401 primarily primarily RB 1401 1402 , , , 1403 1405 if if IN 1406 1409 not not RB 1410 1421 exclusively exclusively RB 1421 1422 , , , 1423 1428 NFATp NFATp NNP 1428 1429 , , , 1430 1433 and and CC 1434 1441 Western western NN 1442 1446 blot blot NN 1447 1455 analysis analysis NN 1456 1461 shows show VBZ 1462 1466 that that IN 1467 1471 this this DT 1472 1475 has have VBZ 1476 1479 the the DT 1480 1484 same same JJ 1485 1500 electrophoretic electrophoretic JJ 1501 1509 mobility mobility NN 1510 1511 ( ( ( 1511 1524 approximately approximately RB 1525 1528 120 120 CD 1529 1531 kD kd NN 1531 1532 ) ) ) 1533 1535 as as IN 1536 1540 that that DT 1541 1543 of of IN 1544 1545 T t NN 1546 1557 lymphocytes lymphocyte NNS 1557 1558 . . . 1559 1561 NK NK NNP 1562 1567 cells cell NNS 1568 1570 do do VBP 1571 1574 not not RB 1575 1582 express express VB 1583 1588 NFATc NFATc NNP 1589 1603 constitutively constitutively RB 1603 1604 , , , 1605 1608 but but CC 1609 1614 NFATc NFATc NNP 1615 1619 mRNA mRNA NNP 1620 1632 accumulation accumulation NN 1633 1635 is be VBZ 1636 1643 induced induce VBN 1644 1646 in in IN 1647 1652 these these DT 1653 1658 cells cell NNS 1659 1665 within within IN 1666 1667 2 2 CD 1668 1669 h h NN 1670 1672 of of IN 1673 1684 stimulation stimulation NN 1685 1689 with with IN 1690 1694 CD16 cd16 NN 1695 1702 ligands ligand NNS 1702 1703 . . . 1704 1711 However however RB 1711 1712 , , , 1713 1723 supershift supershift NN 1724 1730 assays assay NNS 1731 1736 using use VBG 1737 1740 the the DT 1741 1750 available available JJ 1751 1754 mAb mab NN 1755 1766 recognizing recognize VBG 1767 1770 the the DT 1771 1772 T t NN 1773 1777 cell cell NN 1778 1783 NFATc NFATc NNP 1784 1792 revealed reveal VBD 1793 1795 no no DT 1796 1806 detectable detectable JJ 1807 1812 NFATc nfatc NN 1813 1820 protein protein NN 1821 1823 in in IN 1824 1831 nuclear nuclear JJ 1832 1835 and and CC 1836 1847 cytoplasmic cytoplasmic JJ 1848 1856 extracts extract NNS 1857 1861 from from IN 1862 1867 CD16- cd16- NN 1868 1870 or or CC 1871 1878 phorbol phorbol NN 1879 1895 ester-stimulated ester-stimulated JJ 1896 1901 cells cell NNS 1902 1904 at at IN 1905 1908 any any DT 1909 1913 time time NN 1914 1920 tested test VBN 1920 1921 , , , 1922 1924 up up IN 1925 1927 to to TO 1928 1929 4 4 CD 1930 1931 h h NN 1931 1932 . . . 1933 1938 These these DT 1939 1946 results result NNS 1947 1954 provide provide VBP 1955 1958 the the DT 1959 1964 first first JJ 1965 1971 direct direct JJ 1972 1980 evidence evidence NN 1981 1985 that that IN 1986 1990 both both CC 1991 2004 CsA-sensitive csa-sensitive JJ 2005 2018 transcription transcription NN 2019 2026 factors factor NNS 2026 2027 , , , 2028 2033 NFATp NFATp NNP 2034 2037 and and CC 2038 2043 NFATc NFATc NNP 2043 2044 , , , 2045 2048 are be VBP 2049 2058 expressed express VBN 2059 2061 in in IN 2062 2067 human human JJ 2068 2070 NK nk NN 2071 2076 cells cell NNS 2076 2077 , , , 2078 2081 and and CC 2082 2086 that that IN 2087 2092 their their PRP$ 2093 2103 activation activation NN 2104 2110 and/or and/or CC 2111 2121 expression expression NN 2122 2125 can can MD 2126 2128 be be VB 2129 2138 regulated regulate VBN 2139 2141 in in IN 2142 2149 primary primary JJ 2150 2155 cells cell NNS 2156 2158 by by IN 2159 2160 a a DT 2161 2167 single single JJ 2168 2176 stimulus stimulus NN 2176 2177 , , , 2178 2182 that that IN 2182 2183 , , , 2184 2186 in in IN 2187 2190 the the DT 2191 2195 case case NN 2196 2198 of of IN 2199 2203 CD16 CD16 NNP 2204 2206 in in IN 2207 2209 NK NK NNP 2210 2215 cells cell NNS 2215 2216 , , , 2217 2224 results result VBZ 2225 2227 in in IN 2228 2233 early early JJ 2234 2244 activation activation NN 2245 2247 of of IN 2248 2253 NFATp NFATp NNP 2254 2257 and and CC 2258 2270 subsequently subsequently RB 2271 2278 induced induce VBN 2279 2289 expression expression NN 2290 2292 of of IN 2293 2298 NFATc NFATc NNP 2299 2303 mRNA mRNA NNP 2303 2304 . . .