0 15 Phosphorylation phosphorylation NN 16 18 of of IN 19 22 the the DT 23 36 transcription transcription NN 37 43 factor factor NN 44 49 NFATp NFATp NNP 50 58 inhibits inhibit VBZ 59 62 its its PRP$ 63 66 DNA dna NN 67 74 binding binding NN 75 83 activity activity NN 84 86 in in IN 87 98 cyclosporin cyclosporin NN 99 108 A-treated a-treated JJ 109 114 human human JJ 115 116 B b NN 117 120 and and CC 121 122 T t NN 123 128 cells cell NNS 128 129 . . . 131 142 Cyclosporin Cyclosporin NNP 143 144 A A NNP 145 146 ( ( ( 146 149 CsA CsA NNP 149 150 ) ) ) 151 157 exerts exert VBZ 158 161 its its PRP$ 162 179 immunosuppressive immunosuppressive JJ 180 186 effect effect NN 187 189 by by IN 190 200 inhibiting inhibit VBG 201 204 the the DT 205 213 activity activity NN 214 216 of of IN 217 224 nuclear nuclear JJ 225 231 factor factor NN 232 234 of of IN 235 244 activated activate VBN 245 246 T t NN 247 252 cells cell NNS 253 254 ( ( ( 254 258 NFAT NFAT NNP 258 259 ) ) ) 259 260 , , , 261 265 thus thus RB 266 276 preventing prevent VBG 277 292 transcriptional transcriptional JJ 293 302 induction induction NN 303 305 of of IN 306 313 several several JJ 314 322 cytokine cytokine NN 323 328 genes gene NNS 328 329 . . . 330 334 This this DT 335 341 effect effect NN 342 344 is be VBZ 345 352 thought think VBN 353 355 to to TO 356 358 be be VB 359 366 largely largely RB 367 375 mediated mediate VBN 376 383 through through IN 384 396 inactivation inactivation NN 397 399 of of IN 400 403 the the DT 404 415 phosphatase phosphatase NN 416 427 calcineurin calcineurin NN 427 428 , , , 429 434 which which WDT 435 437 in in IN 438 442 turn turn NN 443 451 inhibits inhibit VBZ 452 465 translocation translocation NN 466 468 of of IN 469 471 an an DT 472 476 NFAT NFAT NNP 477 486 component component NN 487 489 to to TO 490 493 the the DT 494 501 nucleus nucleus NN 501 502 . . . 503 507 Here here RB 508 510 we we PRP 511 517 report report VBP 518 522 that that IN 523 526 CsA CsA NNP 527 536 treatment treatment NN 537 539 of of IN 540 544 Raji Raji NNP 545 546 B B NNP 547 550 and and CC 551 557 Jurkat Jurkat NNP 558 559 T t NN 560 564 cell cell NN 565 570 lines line NNS 571 577 yields yield VBZ 578 579 a a DT 580 594 phosphorylated phosphorylated JJ 595 599 form form NN 600 602 of of IN 603 608 NFATp NFATp NNP 609 613 that that WDT 614 616 is be VBZ 617 626 inhibited inhibit VBN 627 629 in in IN 630 641 DNA-binding dna-binding NN 642 645 and and CC 646 648 in in IN 649 652 its its PRP$ 653 660 ability ability NN 661 663 to to TO 664 668 form form VB 669 671 an an DT 672 676 NFAT nfat NN 677 684 complex complex NN 685 689 with with IN 690 693 Fos Fos NNP 694 697 and and CC 698 701 Jun Jun NNP 701 702 . . . 703 713 Immunoblot Immunoblot NNP 714 722 analyses analysis NNS 723 726 and and CC 727 736 metabolic metabolic JJ 737 745 labeling labeling NN 746 750 with with IN 751 752 [ [ ( 752 770 32P]orthophosphate 32P]orthophosphate NNP 771 775 show show VBP 776 780 that that IN 781 784 CsA CsA NNP 785 791 alters alter VBZ 792 797 NFATp NFATp NNP 798 807 migration migration NN 808 810 on on IN 811 829 SDS-polyacrylamide sds-polyacrylamide NN 830 833 gel gel NN 834 849 electrophoresis electrophoresis NN 850 852 by by IN 853 863 increasing increase VBG 864 867 its its PRP$ 868 883 phosphorylation phosphorylation NN 884 889 level level NN 890 897 without without IN 898 907 affecting affect VBG 908 919 subcellular subcellular JJ 920 932 distribution distribution NN 932 933 . . . 934 951 Dephosphorylation dephosphorylation NN 952 954 by by IN 955 957 in in FW 958 963 vitro vitro FW 964 973 treatment treatment NN 974 978 with with IN 979 990 calcineurin calcineurin NN 991 993 or or CC 994 1002 alkaline alkaline NN 1003 1014 phosphatase phosphatase NN 1015 1023 restores restore VBZ 1024 1029 NFATp NFATp NNP 1030 1033 DNA DNA NNP 1034 1041 binding binding NN 1042 1050 activity activity NN 1051 1054 and and CC 1055 1058 its its PRP$ 1059 1066 ability ability NN 1067 1069 to to TO 1070 1082 reconstitute reconstitute VB 1083 1085 an an DT 1086 1090 NFAT nfat NN 1091 1098 complex complex NN 1099 1103 with with IN 1104 1107 Fos Fos NNP 1108 1111 and and CC 1112 1115 Jun Jun NNP 1116 1124 proteins protein NNS 1124 1125 . . . 1126 1131 These these DT 1132 1136 data datum NNS 1137 1142 point point VBP 1143 1145 to to TO 1146 1147 a a DT 1148 1151 new new JJ 1152 1161 mechanism mechanism NN 1162 1165 for for IN 1166 1179 CsA-sensitive csa-sensitive JJ 1180 1190 regulation regulation NN 1191 1193 of of IN 1194 1199 NFATp NFATp NNP 1200 1202 in in IN 1203 1208 which which WDT 1209 1226 dephosphorylation dephosphorylation NN 1227 1229 is be VBZ 1230 1238 critical critical JJ 1239 1242 for for IN 1243 1246 DNA DNA NNP 1247 1254 binding binding NN 1254 1255 . . .