0 7 Calcium calcium NN 8 18 signalling signalling NN 19 21 in in IN 22 23 T t NN 24 29 cells cell NNS 30 40 stimulated stimulate VBN 41 43 by by IN 44 45 a a DT 46 57 cyclophilin cyclophilin NN 58 67 B-binding b-binding JJ 68 75 protein protein NN 75 76 . . . 78 81 The the DT 82 99 immunosuppressant immunosuppressant JJ 100 104 drug drug NN 105 116 cyclosporin cyclosporin NN 117 118 A a NN 119 125 blocks block VBZ 126 127 a a DT 128 145 calcium-dependent calcium-dependent JJ 146 152 signal signal NN 153 157 from from IN 158 161 the the DT 162 168 T-cell t-cell NN 169 177 receptor receptor NN 178 179 ( ( ( 179 182 TCR TCR NNP 182 183 ) ) ) 184 188 that that WDT 189 197 normally normally RB 198 203 leads lead VBZ 204 206 to to TO 207 213 T-cell t-cell NN 214 224 activation activation NN 224 225 . . . 226 230 When when WRB 231 236 bound bind VBN 237 239 to to TO 240 251 cyclophilin cyclophilin NN 251 252 , , , 253 264 cyclosporin cyclosporin NN 265 266 A a NN 267 272 binds bind VBZ 273 276 and and CC 277 288 inactivates inactivate VBZ 289 292 the the DT 293 296 key key JJ 297 307 signalling signalling NN 308 320 intermediate intermediate JJ 321 332 calcineurin calcineurin NN 332 333 . . . 334 336 To to TO 337 345 identify identify VB 346 355 potential potential JJ 356 364 cellular cellular JJ 365 375 homologues homologue NNS 376 378 of of IN 379 390 cyclosporin cyclosporin NN 391 392 A a NN 393 397 that that WDT 398 403 might might MD 404 412 regulate regulate VB 413 420 calcium calcium NN 421 431 signalling signalling NN 431 432 , , , 433 435 we we PRP 436 440 have have VBP 441 447 cloned clone VBN 448 453 human human JJ 454 459 genes gene NNS 460 468 encoding encode VBG 469 480 cyclophilin cyclophilin NN 481 499 B-binding-proteins B-binding-protein NNPS 500 505 using use VBG 506 509 the the DT 510 515 yeast yeast NN 516 526 two-hybrid two-hybrid JJ 527 533 system system NN 533 534 . . . 535 538 One one CD 539 543 gene gene NN 544 551 product product NN 551 552 , , , 553 557 when when WRB 558 571 overexpressed overexpresse VBN 572 574 in in IN 575 581 Jurkat Jurkat NNP 582 583 T t NN 584 589 cells cell NNS 589 590 , , , 591 603 specifically specifically RB 604 611 induced induce VBD 612 625 transcription transcription NN 626 630 from from IN 631 634 the the DT 635 648 interleukin-2 interleukin-2 NN 649 657 enhancer enhancer NN 657 658 , , , 659 661 by by IN 662 672 activating activate VBG 673 676 the the DT 677 692 T-cell-specific t-cell-specific JJ 693 706 transcription transcription NN 707 714 factors factor NNS 715 720 NF-AT NF-AT NNP 721 724 and and CC 725 732 NF-IL2A NF-IL2A NNP 732 733 . . . 734 738 This this DT 739 746 protein protein NN 746 747 , , , 748 754 termed term VBN 755 769 calcium-signal calcium-signal JJ 770 780 modulating modulate VBG 781 792 cyclophilin cyclophilin NN 793 799 ligand ligand NN 800 801 ( ( ( 801 805 CAML CAML NNP 805 806 ) ) ) 806 807 , , , 808 812 acts act VBZ 813 823 downstream downstream RB 824 826 of of IN 827 830 the the DT 831 834 TCR TCR NNP 835 838 and and CC 839 847 upstream upstream RB 848 850 of of IN 851 862 calcineurin calcineurin NN 863 865 by by IN 866 873 causing cause VBG 874 876 an an DT 877 883 influx influx NN 884 886 of of IN 887 894 calcium calcium NN 894 895 . . . 896 900 CAML CAML NNP 901 908 appears appear VBZ 909 911 to to TO 912 914 be be VB 915 916 a a DT 917 920 new new JJ 921 932 participant participant NN 933 935 in in IN 936 939 the the DT 940 954 calcium-signal calcium-signal JJ 955 967 transduction transduction NN 968 975 pathway pathway NN 975 976 , , , 977 988 implicating implicate VBG 989 1000 cyclophilin cyclophilin NN 1001 1002 B b NN 1003 1005 in in IN 1006 1013 calcium calcium NN 1014 1024 signalling signalling NN 1024 1025 , , , 1026 1030 even even RB 1031 1033 in in IN 1034 1037 the the DT 1038 1045 absence absence NN 1046 1048 of of IN 1049 1060 cyclosporin cyclosporin NN 1060 1061 . . .