0 16 Interferon-alpha Interferon-alpha NNP 17 26 induction induction NN 27 29 of of IN 30 36 STATs1 STATs1 NNP 36 37 , , , 38 40 -3 -3 CD 41 44 DNA dna NN 45 52 binding binding NN 53 56 and and CC 57 63 growth growth NN 64 70 arrest arrest NN 71 73 is be VBZ 74 85 independent independent JJ 86 88 of of IN 89 92 Lck Lck NNP 93 96 and and CC 97 103 active active JJ 104 121 mitogen-activated mitogen-activated JJ 122 128 kinase kinase NN 129 131 in in IN 132 133 T t NN 134 139 cells cell NNS 139 140 . . . 142 146 Type type NN 147 148 I i CD 149 160 interferons interferon NNS 161 162 ( ( ( 162 166 IFNs IFN NNPS 166 167 ) ) ) 168 171 are be VBP 172 173 a a DT 174 180 family family NN 181 183 of of IN 184 193 cytokines cytokine NNS 194 198 that that WDT 199 203 have have VBP 204 213 antiviral antiviral JJ 214 217 and and CC 218 235 antiproliferative antiproliferative JJ 236 243 effects effect NNS 243 244 . . . 245 249 Data Datum NNP 250 259 regarding regard VBG 260 263 the the DT 264 273 processes process NNS 274 276 by by IN 277 282 which which WDT 283 288 these these DT 289 298 cytokines cytokine NNS 299 308 transduce transduce VBP 309 316 signals signal NNS 317 321 from from IN 322 325 the the DT 326 330 cell cell NN 331 339 membrane membrane NN 340 342 to to TO 343 346 the the DT 347 354 nucleus nucleus NN 355 358 are be VBP 359 367 becoming become VBG 368 380 increasingly increasingly RB 381 388 complex complex JJ 388 389 . . . 390 393 The the DT 394 398 most most JJS 399 412 characterized characterize VBN 413 420 pathway pathway NN 421 423 is be VBZ 424 427 via via IN 428 436 JAK-STAT JAK-STAT NNP 437 446 signaling signaling NN 446 447 . . . 448 456 Previous previous JJ 457 464 studies study NNS 465 476 established establish VBD 477 478 a a DT 479 488 potential potential JJ 489 493 role role NN 494 497 for for IN 498 501 the the DT 502 512 Src-family Src-family NNP 513 519 kinase kinase NNP 520 523 Lck Lck NNP 524 526 in in IN 527 535 JAK-STAT JAK-STAT NNP 536 545 signaling signaling NN 545 546 . . . 547 556 Therefore therefore RB 556 557 , , , 558 562 this this DT 563 568 study study NN 569 572 was be VBD 573 581 designed design VBN 582 584 to to TO 585 592 analyze analyze VB 593 596 the the DT 597 601 role role NN 602 604 of of IN 605 608 Lck Lck NNP 609 611 in in IN 612 621 IFN-alpha IFN-alpha NNP 622 631 signaling signaling NN 632 634 by by IN 635 640 using use VBG 641 644 the the DT 645 651 Jurkat Jurkat NNP 651 652 , , , 653 657 JCam JCam NNP 658 659 ( ( ( 659 661 an an DT 662 675 Lck-defective lck-defective JJ 676 680 cell cell NN 681 685 line line NN 686 693 derived derive VBN 694 698 from from IN 699 705 Jurkat Jurkat NNP 705 706 ) ) ) 706 707 , , , 708 711 and and CC 712 720 JCam/Lck JCam/Lck NNP 721 722 ( ( ( 722 726 JCam JCam NNP 727 732 cells cell NNS 733 737 with with IN 738 741 Lck Lck NNP 742 750 restored restore VBN 750 751 ) ) ) 751 752 . . . 753 756 The the DT 757 764 results result NNS 765 769 show show VBP 770 774 that that IN 775 784 IFN-alpha IFN-alpha NNP 785 788 can can MD 789 795 induce induce VB 796 800 MAPK MAPK NNP 801 809 activity activity NN 809 810 , , , 811 814 but but CC 815 819 only only RB 820 822 in in IN 823 828 cells cell NNS 829 839 containing contain VBG 840 843 Lck Lck NNP 843 844 . . . 845 856 Furthermore furthermore RB 856 857 , , , 858 864 STATs1 STATs1 NNP 865 868 and and CC 869 871 -3 -3 CD 872 875 are be VBP 876 887 effectively effectively RB 888 902 phosphorylated phosphorylate VBN 903 906 and and CC 907 916 activated activate VBN 917 919 to to TO 920 924 bind bind VB 925 928 DNA dna NN 929 931 in in IN 932 935 the the DT 936 943 absence absence NN 944 946 of of IN 947 950 Lck Lck NNP 951 961 expression expression NN 962 964 in in IN 965 982 IFN-alpha-treated ifn-alpha-treated JJ 983 988 cells cell NNS 988 989 . . . 990 997 Finally finally RB 997 998 , , , 999 1002 the the DT 1003 1010 results result NNS 1011 1022 demonstrate demonstrate VBP 1023 1027 that that IN 1028 1037 IFN-alpha IFN-alpha NNP 1038 1044 exerts exert VBZ 1045 1047 an an DT 1048 1065 antiproliferative antiproliferative JJ 1066 1072 effect effect NN 1073 1075 in in IN 1076 1079 all all DT 1080 1085 three three CD 1086 1090 cell cell NN 1091 1096 lines line NNS 1096 1097 . . . 1098 1103 These these DT 1104 1108 data datum NNS 1109 1117 indicate indicate VBP 1118 1122 that that IN 1123 1126 Lck Lck NNP 1127 1130 and and CC 1131 1137 active active JJ 1138 1142 MAPK mapk NN 1143 1145 do do VBP 1146 1149 not not RB 1150 1156 affect affect VB 1157 1174 IFN-alpha-induced ifn-alpha-induced JJ 1175 1181 growth growth NN 1182 1188 arrest arrest NN 1189 1191 or or CC 1192 1201 induction induction NN 1202 1204 of of IN 1205 1212 STAT1s1 STAT1s1 NNP 1213 1216 and and CC 1217 1219 -3 -3 CD 1220 1223 DNA dna NN 1224 1231 binding binding NN 1232 1239 ability ability NN 1239 1240 . . . 1241 1250 Copyright Copyright NNP 1251 1255 1999 1999 CD 1256 1264 Academic Academic NNP 1265 1270 Press Press NNP 1270 1271 . . .