0 9 Signaling signaling NN 10 16 events event NNS 17 24 induced induce VBN 25 27 by by IN 28 56 lipopolysaccharide-activated lipopolysaccharide-activated JJ 57 66 toll-like toll-like JJ 67 75 receptor receptor NN 76 77 2 2 CD 77 78 . . . 80 85 Human human JJ 86 95 Toll-like toll-like JJ 96 104 receptor receptor NN 105 106 2 2 CD 107 108 ( ( ( 108 112 TLR2 tlr2 NN 112 113 ) ) ) 114 116 is be VBZ 117 118 a a DT 119 128 signaling signaling NN 129 137 receptor receptor NN 138 142 that that WDT 143 151 responds respond VBZ 152 154 to to TO 155 158 LPS lps NN 159 162 and and CC 163 172 activates activate VBZ 173 182 NF-kappaB NF-kappaB NNP 182 183 . . . 184 188 Here here RB 188 189 , , , 190 192 we we PRP 193 204 investigate investigate VBP 205 212 further further RBR 213 216 the the DT 217 223 events event NNS 224 233 triggered trigger VBN 234 236 by by IN 237 241 TLR2 tlr2 NN 242 244 in in IN 245 253 response response NN 254 256 to to TO 257 260 LPS LPS NNP 260 261 . . . 262 264 We we PRP 265 269 show show VBP 270 274 that that IN 275 279 TLR2 tlr2 NN 280 290 associates associate VBZ 291 295 with with IN 296 299 the the DT 300 313 high-affinity high-affinity JJ 314 317 LPS lps NN 318 325 binding binding NN 326 333 protein protein NN 334 342 membrane membrane NN 343 347 CD14 cd14 NN 348 350 to to TO 351 356 serve serve VB 357 359 as as IN 360 362 an an DT 363 366 LPS LPS NNP 367 375 receptor receptor NN 376 383 complex complex NN 383 384 , , , 385 388 and and CC 389 393 that that IN 394 397 LPS LPS NNP 398 407 treatment treatment NN 408 416 enhances enhance VBZ 417 420 the the DT 421 436 oligomerization oligomerization NN 437 439 of of IN 440 444 TLR2 tlr2 NN 444 445 . . . 446 457 Concomitant concomitant JJ 458 462 with with IN 463 471 receptor receptor NN 472 487 oligomerization oligomerization NN 487 488 , , , 489 492 the the DT 493 509 IL-1R-associated il-1r-associated JJ 510 516 kinase kinase NNP 517 518 ( ( ( 518 522 IRAK IRAK NNP 522 523 ) ) ) 524 526 is be VBZ 527 536 recruited recruit VBN 537 539 to to TO 540 543 the the DT 544 548 TLR2 tlr2 NN 549 556 complex complex NN 556 557 . . . 558 571 Intracellular intracellular JJ 572 580 deletion deletion NN 581 589 variants variant NNS 590 592 of of IN 593 597 TLR2 tlr2 NN 598 605 lacking lack VBG 606 616 C-terminal c-terminal JJ 617 619 13 13 CD 620 622 or or CC 623 626 141 141 CD 627 629 aa aa NN 630 634 fail fail VBP 635 637 to to TO 638 645 recruit recruit VB 646 650 IRAK IRAK NNP 650 651 , , , 652 657 which which WDT 658 660 is be VBZ 661 671 consistent consistent JJ 672 676 with with IN 677 680 the the DT 681 690 inability inability NN 691 693 of of IN 694 699 these these DT 700 707 mutants mutant NNS 708 710 to to TO 711 719 transmit transmit VB 720 723 LPS LPS NNP 724 732 cellular cellular JJ 733 742 signaling signaling NN 742 743 . . . 744 752 Moreover moreover RB 752 753 , , , 754 758 both both DT 759 767 deletion deletion NN 768 775 mutants mutant NNS 776 781 could could MD 782 787 still still RB 788 792 form form VB 793 802 complexes complex NNS 803 807 with with IN 808 817 wild-type wild-type JJ 818 822 TLR2 tlr2 NN 823 826 and and CC 827 830 act act VBP 831 833 in in IN 834 835 a a DT 836 853 dominant-negative dominant-negative JJ 854 855 ( ( ( 855 857 DN dn JJ 857 858 ) ) ) 859 866 fashion fashion NN 867 869 to to TO 870 875 block block VB 876 889 TLR2-mediated tlr2-mediated JJ 890 896 signal signal NN 897 909 transduction transduction NN 909 910 . . . 911 913 DN dn JJ 914 924 constructs construct NNS 925 927 of of IN 928 935 myeloid myeloid JJ 936 951 differentiation differentiation NN 952 959 protein protein NN 959 960 , , , 961 965 IRAK IRAK NNP 965 966 , , , 967 970 TNF TNF NNP 971 990 receptor-associated receptor-associated JJ 991 997 factor factor NN 998 999 6 6 CD 999 1000 , , , 1001 1004 and and CC 1005 1023 NF-kappaB-inducing NF-kappaB-inducing NNP 1024 1030 kinase kinase NNP 1030 1031 , , , 1032 1036 when when WRB 1037 1048 coexpressed coexpresse VBN 1049 1053 with with IN 1054 1058 TLR2 TLR2 NNP 1058 1059 , , , 1060 1068 abrogate abrogate VBP 1069 1082 TLR2-mediated tlr2-mediated JJ 1083 1092 NF-kappaB NF-kappaB NNP 1093 1103 activation activation NN 1103 1104 . . . 1105 1110 These these DT 1111 1118 results result NNS 1119 1125 reveal reveal VBP 1126 1127 a a DT 1128 1137 conserved conserve VBN 1138 1147 signaling signaling NN 1148 1155 pathway pathway NN 1156 1159 for for IN 1160 1164 TLR2 TLR2 NNP 1165 1168 and and CC 1169 1175 IL-1Rs IL-1R NNP 1176 1179 and and CC 1180 1187 suggest suggest VBP 1188 1189 a a DT 1190 1199 molecular molecular JJ 1200 1209 mechanism mechanism NN 1210 1213 for for IN 1214 1217 the the DT 1218 1228 inhibition inhibition NN 1229 1231 of of IN 1232 1236 TLR2 tlr2 NN 1237 1239 by by IN 1240 1242 DN dn JJ 1243 1251 variants variant NNS 1251 1252 . . .