0 7 Effects Effect NNPS 8 10 of of IN 11 25 overexpression overexpression NN 26 28 of of IN 29 33 IL-1 il-1 NN 34 53 receptor-associated receptor-associated JJ 54 60 kinase kinase NNP 61 63 on on IN 64 72 NFkappaB NFkappaB NNP 73 83 activation activation NN 83 84 , , , 85 89 IL-2 il-2 NN 90 100 production production NN 101 104 and and CC 105 121 stress-activated stress-activated JJ 122 129 protein protein NN 130 137 kinases kinase NNS 138 140 in in IN 141 144 the the DT 145 151 murine murine JJ 152 153 T t NN 154 158 cell cell NN 159 163 line line NN 164 167 EL4 el4 NN 167 168 . . . 170 173 The the DT 174 185 association association NN 186 189 and and CC 190 200 activation activation NN 201 203 of of IN 204 207 the the DT 208 212 IL-1 il-1 NN 213 232 receptor-associated receptor-associated JJ 233 240 protein protein NN 241 247 kinase kinase NNP 248 249 ( ( ( 249 253 IRAK IRAK NNP 253 254 ) ) ) 255 257 to to TO 258 261 the the DT 262 266 IL-1 il-1 NN 267 275 receptor receptor NN 276 283 complex complex NN 284 286 is be VBZ 287 290 one one CD 291 293 of of IN 294 297 the the DT 298 306 earliest early JJS 307 313 events event NNS 314 324 detectable detectable JJ 325 327 in in IN 328 332 IL-1 il-1 NN 333 339 signal signal NN 340 352 transduction transduction NN 352 353 . . . 354 356 We we PRP 357 366 generated generate VBD 367 376 permanent permanent JJ 377 383 clones clone NNS 384 386 of of IN 387 390 the the DT 391 397 murine murine JJ 398 399 T t NN 400 404 cell cell NN 405 409 line line NN 410 413 EL4 el4 NN 414 417 6.1 6.1 CD 418 432 overexpressing overexpresse VBG 433 438 human human JJ 439 440 ( ( ( 440 446 h)IRAK h)irak NN 447 449 to to TO 450 458 evaluate evaluate VB 459 462 the the DT 463 467 role role NN 468 470 of of IN 471 475 this this DT 476 482 kinase kinase NNP 483 485 in in IN 486 490 IL-1 il-1 NN 491 500 signaling signaling NN 500 501 . . . 502 516 Overexpression overexpression NN 517 519 of of IN 520 525 hIRAK hirak NN 526 534 enhanced enhance VBD 535 550 IL-1-stimulated il-1-stimulated JJ 551 561 activation activation NN 562 564 of of IN 565 568 the the DT 569 582 transcription transcription NN 583 589 factor factor NN 590 598 NFkappaB NFkappaB NNP 598 599 , , , 600 607 whereas whereas IN 608 609 a a DT 610 619 truncated truncate VBN 620 624 form form NN 625 626 ( ( ( 626 632 N-IRAK N-IRAK NNP 632 633 ) ) ) 634 646 specifically specifically RB 647 656 inhibited inhibit VBD 657 671 IL-1-dependent il-1-dependent JJ 672 680 NFkappaB NFkappaB NNP 681 689 activity activity NN 689 690 . . . 691 693 In in IN 694 700 clones clone NNS 701 707 stably stably RB 708 722 overexpressing overexpresse VBG 723 728 hIRAK hirak NN 729 730 a a DT 731 735 weak weak JJ 736 748 constitutive constitutive JJ 749 759 activation activation NN 760 762 of of IN 763 771 NFkappaB NFkappaB NNP 772 782 correlated correlate VBD 783 787 with with IN 788 789 a a DT 790 793 low low JJ 794 799 basal basal JJ 800 804 IL-2 il-2 NN 805 815 production production NN 816 821 which which WDT 822 825 was be VBD 826 834 enhanced enhance VBN 835 837 in in IN 838 840 an an DT 841 855 IL-1-dependent il-1-dependent JJ 856 862 manner manner NN 862 863 . . . 864 872 Compared compare VBN 873 875 to to TO 876 879 the the DT 880 888 parental parental JJ 889 893 cell cell NN 894 898 line line NN 899 902 the the DT 903 916 dose-response dose-response JJ 917 922 curve curve NN 923 925 of of IN 926 938 IL-1-induced il-1-induced JJ 939 943 IL-2 il-2 NN 944 954 production production NN 955 958 was be VBD 959 966 shifted shift VBN 967 969 in in IN 970 974 both both CC 975 982 potency potency NN 983 986 and and CC 987 995 efficacy efficacy NN 995 996 . . . 997 1002 These these DT 1003 1010 results result NNS 1011 1022 demonstrate demonstrate VBP 1023 1027 that that IN 1028 1032 IRAK IRAK NNP 1033 1041 directly directly RB 1042 1050 triggers trigger VBZ 1051 1068 NFkappaB-mediated nfkappab-mediated JJ 1069 1073 gene gene NN 1074 1084 expression expression NN 1085 1087 in in IN 1088 1091 EL4 el4 NN 1092 1097 cells cell NNS 1097 1098 . . . 1099 1112 Qualitatively qualitatively RB 1113 1122 different different JJ 1123 1130 effects effect NNS 1131 1135 were be VBD 1136 1144 observed observe VBN 1145 1148 for for IN 1149 1152 the the DT 1153 1165 IL-1-induced il-1-induced JJ 1166 1176 activation activation NN 1177 1179 of of IN 1180 1196 stress-activated stress-activated JJ 1197 1204 protein protein NN 1205 1206 ( ( ( 1206 1209 SAP SAP NNP 1209 1210 ) ) ) 1211 1218 kinases kinase NNS 1218 1219 : : : 1220 1229 permanent permanent JJ 1230 1244 overexpression overexpression NN 1245 1247 of of IN 1248 1252 IRAK IRAK NNP 1253 1256 did do VBD 1257 1260 not not RB 1261 1267 affect affect VB 1268 1271 the the DT 1272 1276 dose dose NN 1277 1287 dependence dependence NN 1288 1291 but but CC 1292 1301 prolonged prolong VBD 1302 1305 the the DT 1306 1314 kinetics kinetic NNS 1315 1317 of of IN 1318 1330 IL-1-induced il-1-induced JJ 1331 1341 activation activation NN 1342 1344 of of IN 1345 1348 SAP SAP NNP 1349 1356 kinases kinase NNS 1356 1357 , , , 1358 1368 suggesting suggest VBG 1369 1373 that that IN 1374 1378 this this DT 1379 1388 signaling signaling NN 1389 1395 branch branch NN 1396 1399 may may MD 1400 1402 be be VB 1403 1412 regulated regulate VBN 1413 1415 by by IN 1416 1424 distinct distinct JJ 1425 1435 mechanisms mechanism NNS 1435 1436 . . .