0 11 Calcineurin Calcineurin NNP 12 23 potentiates potentiate VBZ 24 34 activation activation NN 35 37 of of IN 38 41 the the DT 42 64 granulocyte-macrophage granulocyte-macrophage JJ 65 83 colony-stimulating colony-stimulating JJ 84 90 factor factor NN 91 95 gene gene NN 96 98 in in IN 99 100 T t NN 101 106 cells cell NNS 106 107 : : : 108 119 involvement involvement NN 120 122 of of IN 123 126 the the DT 127 136 conserved conserve VBN 137 147 lymphokine lymphokine NN 148 155 element element NN 156 157 0 0 CD 157 158 . . . 160 182 Granulocyte-macrophage granulocyte-macrophage JJ 183 201 colony-stimulating colony-stimulating JJ 202 208 factor factor NN 209 210 ( ( ( 210 216 GM-CSF GM-CSF NNP 216 217 ) ) ) 218 221 and and CC 222 235 interleukin-2 interleukin-2 NN 236 237 ( ( ( 237 241 IL-2 il-2 NN 241 242 ) ) ) 243 246 are be VBP 247 255 produced produce VBN 256 258 by by IN 259 270 stimulation stimulation NN 271 275 with with IN 276 296 phorbol-12-myristate phorbol-12-myristate NN 297 304 acetate acetate NN 305 306 ( ( ( 306 309 PMA PMA NNP 309 310 ) ) ) 311 314 and and CC 315 322 calcium calcium NN 323 332 ionophore ionophore NN 333 334 ( ( ( 334 340 A23187 a23187 NN 340 341 ) ) ) 342 344 in in IN 345 350 human human JJ 351 352 T t NN 353 357 cell cell NN 358 366 leukemia leukemia NN 367 373 Jurkat Jurkat NNP 374 379 cells cell NNS 379 380 . . . 381 384 The the DT 385 395 expression expression NN 396 398 of of IN 399 405 GM-CSF GM-CSF NNP 406 409 and and CC 410 414 IL-2 IL-2 NNP 415 417 is be VBZ 418 427 inhibited inhibit VBN 428 430 by by IN 431 448 immunosuppressive immunosuppressive JJ 449 454 drugs drug NNS 455 459 such such JJ 460 462 as as IN 463 474 cyclosporin cyclosporin NN 475 476 A A NNP 477 478 ( ( ( 478 481 CsA CsA NNP 481 482 ) ) ) 483 486 and and CC 487 492 FK506 FK506 NNP 492 493 . . . 494 501 Earlier early JJR 502 509 studies study NNS 510 512 on on IN 513 516 the the DT 517 521 IL-2 il-2 NN 522 526 gene gene NN 527 537 expression expression NN 538 544 showed show VBD 545 549 that that IN 550 564 overexpression overexpression NN 565 567 of of IN 568 579 calcineurin calcineurin NN 580 581 ( ( ( 581 583 CN CN NNP 583 584 ) ) ) 584 585 , , , 586 587 a a DT 588 613 Ca2+/calmodulin-dependent ca2+/calmodulin-dependent JJ 614 621 protein protein NN 622 633 phosphatase phosphatase NN 633 634 , , , 635 638 can can MD 639 648 stimulate stimulate VB 649 662 transcription transcription NN 663 667 from from IN 668 671 the the DT 672 676 IL-2 il-2 NN 677 685 promoter promoter NN 686 693 through through IN 694 697 the the DT 698 711 NF-AT-binding nf-at-binding JJ 712 716 site site NN 716 717 . . . 718 720 In in IN 721 725 this this DT 726 731 study study NN 731 732 , , , 733 735 we we PRP 736 744 obtained obtain VBD 745 753 evidence evidence NN 754 758 that that IN 759 771 transfection transfection NN 772 774 of of IN 775 778 the the DT 779 784 cDNAs cdna NNS 785 788 for for IN 789 791 CN CN NNP 792 793 A A NNP 794 795 ( ( ( 795 804 catalytic catalytic JJ 804 805 ) ) ) 806 809 and and CC 810 812 CN CN NNP 813 814 B B NNP 815 816 ( ( ( 816 826 regulatory regulatory JJ 826 827 ) ) ) 828 836 subunits subunit NNS 837 841 also also RB 842 850 augments augment VBZ 851 864 transcription transcription NN 865 869 from from IN 870 873 the the DT 874 880 GM-CSF GM-CSF NNP 881 889 promoter promoter NN 890 893 and and CC 894 902 recovers recover VBZ 903 906 the the DT 907 920 transcription transcription NN 921 930 inhibited inhibit VBN 931 933 by by IN 934 937 CsA CsA NNP 937 938 . . . 939 942 The the DT 943 957 constitutively constitutively RB 958 964 active active JJ 965 969 type type NN 970 972 of of IN 973 976 the the DT 977 979 CN CN NNP 980 981 A a NN 982 989 subunit subunit NN 989 990 , , , 991 996 which which WDT 997 1002 lacks lack VBZ 1003 1006 the the DT 1007 1022 auto-inhibitory auto-inhibitory JJ 1023 1026 and and CC 1027 1045 calmodulin-binding calmodulin-binding JJ 1046 1053 domains domain NNS 1053 1054 , , , 1055 1059 acts act VBZ 1060 1062 in in IN 1063 1070 synergy synergy NN 1071 1075 with with IN 1076 1079 PMA PMA NNP 1080 1082 to to TO 1083 1091 activate activate VB 1092 1105 transcription transcription NN 1106 1110 from from IN 1111 1114 the the DT 1115 1121 GM-CSF GM-CSF NNP 1122 1130 promoter promoter NN 1130 1131 . . . 1132 1134 We we PRP 1135 1139 also also RB 1140 1145 found find VBD 1146 1150 that that IN 1151 1154 the the DT 1155 1161 active active JJ 1162 1164 CN cn NN 1165 1174 partially partially RB 1175 1183 replaces replace VBZ 1184 1191 calcium calcium NN 1192 1201 ionophore ionophore NN 1202 1204 in in IN 1205 1212 synergy synergy NN 1213 1217 with with IN 1218 1221 PMA PMA NNP 1222 1224 to to TO 1225 1231 induce induce VB 1232 1242 expression expression NN 1243 1245 of of IN 1246 1256 endogenous endogenous JJ 1257 1263 GM-CSF GM-CSF NNP 1264 1267 and and CC 1268 1272 IL-2 IL-2 NNP 1272 1273 . . . 1274 1276 By by IN 1277 1290 multimerizing multimerize VBG 1291 1294 the the DT 1295 1305 regulatory regulatory JJ 1306 1314 elements element NNS 1315 1317 of of IN 1318 1321 the the DT 1322 1328 GM-CSF GM-CSF NNP 1329 1337 promoter promoter NN 1337 1338 , , , 1339 1341 we we PRP 1342 1347 found find VBD 1348 1352 that that IN 1353 1356 one one CD 1357 1359 of of IN 1360 1363 the the DT 1364 1370 target target NN 1371 1376 sites site NNS 1377 1380 for for IN 1381 1384 the the DT 1385 1387 CN CN NNP 1388 1394 action action NN 1395 1397 is be VBZ 1398 1401 the the DT 1402 1411 conserved conserve VBN 1412 1422 lymphokine lymphokine NN 1423 1430 element element NN 1431 1432 0 0 CD 1433 1434 ( ( ( 1434 1438 CLE0 CLE0 NNP 1438 1439 ) ) ) 1439 1440 , , , 1441 1448 located located JJ 1449 1451 at at IN 1452 1461 positions position NNS 1462 1469 between between IN 1470 1473 -54 -54 CD 1474 1477 and and CC 1478 1481 -40 -40 CD 1481 1482 . . . 1483 1491 Mobility mobility NN 1492 1497 shift shift NN 1498 1504 assays assay NNS 1505 1511 showed show VBD 1512 1516 that that IN 1517 1520 the the DT 1521 1525 CLE0 cle0 NN 1526 1534 sequence sequence NN 1535 1538 has have VBZ 1539 1541 an an DT 1542 1553 AP1-binding ap1-binding JJ 1554 1558 site site NN 1559 1562 and and CC 1563 1565 is be VBZ 1566 1576 associated associate VBN 1577 1581 with with IN 1582 1584 an an DT 1585 1595 NF-AT-like nf-at-like JJ 1596 1602 factor factor NN 1602 1603 , , , 1604 1610 termed term VBN 1611 1618 NF-CLE0 nf-cle0 NN 1619 1624 gamma gamma NN 1624 1625 . . . 1626 1633 NF-CLE0 NF-CLE0 NNP 1634 1639 gamma gamma NN 1640 1647 binding binding NN 1648 1650 is be VBZ 1651 1658 induced induce VBN 1659 1661 by by IN 1662 1672 PMA/A23187 PMA/A23187 NNP 1673 1676 and and CC 1677 1679 is be VBZ 1680 1689 inhibited inhibit VBN 1690 1692 by by IN 1693 1702 treatment treatment NN 1703 1707 with with IN 1708 1711 CsA CsA NNP 1711 1712 . . . 1713 1718 These these DT 1719 1726 results result NNS 1727 1734 suggest suggest VBP 1735 1739 that that IN 1740 1742 CN CN NNP 1743 1745 is be VBZ 1746 1754 involved involve VBN 1755 1757 in in IN 1758 1761 the the DT 1762 1773 coordinated coordinate VBN 1774 1783 induction induction NN 1784 1786 of of IN 1787 1790 the the DT 1791 1797 GM-CSF GM-CSF NNP 1798 1801 and and CC 1802 1806 IL-2 il-2 NN 1807 1812 genes gene NNS 1813 1816 and and CC 1817 1821 that that IN 1822 1825 the the DT 1826 1830 CLE0 cle0 NN 1831 1839 sequence sequence NN 1840 1842 of of IN 1843 1846 the the DT 1847 1853 GM-CSF GM-CSF NNP 1854 1858 gene gene NN 1859 1861 is be VBZ 1862 1863 a a DT 1864 1874 functional functional JJ 1875 1883 analogue analogue NN 1884 1886 of of IN 1887 1890 the the DT 1891 1904 NF-AT-binding nf-at-binding JJ 1905 1909 site site NN 1910 1912 in in IN 1913 1916 the the DT 1917 1921 IL-2 il-2 NN 1922 1930 promoter promoter NN 1930 1931 , , , 1932 1937 which which WDT 1938 1946 mediates mediate VBZ 1947 1954 signals signal NNS 1955 1965 downstream downstream RB 1966 1968 of of IN 1969 1970 T t NN 1971 1975 cell cell NN 1976 1986 activation activation NN 1986 1987 . . .