0 3 CD2 cd2 NN 4 14 signalling signalling NN 15 22 induces induce VBZ 23 38 phosphorylation phosphorylation NN 39 41 of of IN 42 46 CREB CREB NNP 47 49 in in IN 50 57 primary primary JJ 58 69 lymphocytes lymphocyte NNS 69 70 . . . 72 80 Promoter promoter NN 81 90 sequences sequence NNS 91 101 responsive responsive JJ 102 104 to to TO 105 111 cyclic cyclic JJ 112 115 AMP AMP NNP 116 117 ( ( ( 117 121 cAMP cAMP NNP 121 122 ) ) ) 123 126 are be VBP 127 132 found find VBN 133 135 in in IN 136 137 a a DT 138 144 number number NN 145 147 of of IN 148 156 cellular cellular JJ 157 162 genes gene NNS 162 163 , , , 164 167 and and CC 168 172 bind bind VBP 173 186 transcription transcription NN 187 194 factors factor NNS 195 197 of of IN 198 201 the the DT 202 206 cAMP camp NN 207 215 response response NN 216 223 element element NN 224 231 binding binding NN 232 239 protein protein NN 240 241 ( ( ( 241 257 CREB)/activating creb)/activate VBG 258 271 transcription transcription NN 272 280 factor-1 factor-1 NN 281 282 ( ( ( 282 287 ATF-1 atf-1 NN 287 288 ) ) ) 289 295 family family NN 295 296 . . . 297 299 We we PRP 300 304 have have VBP 305 309 used use VBN 310 311 a a DT 312 317 human human JJ 318 332 T-lymphotropic t-lymphotropic JJ 333 338 virus virus NN 339 343 type type NN 344 345 1 1 CD 346 347 ( ( ( 347 353 HTLV-1 HTLV-1 NNP 353 354 ) ) ) 355 360 model model NN 361 363 of of IN 364 368 cAMP camp NN 369 377 response response NN 378 385 element element NN 386 387 ( ( ( 387 390 CRE CRE NNP 390 391 ) ) ) 392 405 transcription transcription NN 406 408 to to TO 409 420 investigate investigate VB 421 424 the the DT 425 434 influence influence NN 435 437 of of IN 438 448 lymphocyte lymphocyte NN 449 459 activation activation NN 460 462 on on IN 463 476 transcription transcription NN 477 481 from from IN 482 492 homologous homologous JJ 493 500 regions region NNS 501 503 in in IN 504 507 the the DT 508 513 viral viral JJ 514 522 promoter promoter NN 522 523 . . . 524 526 We we PRP 527 537 previously previously RB 538 550 demonstrated demonstrate VBD 551 560 increased increase VBN 561 567 HTLV-1 htlv-1 NN 568 581 transcription transcription NN 582 591 following follow VBG 592 595 CD2 cd2 NN 596 599 but but CC 600 603 not not RB 604 607 CD3 cd3 NN 608 616 receptor receptor NN 617 630 cross-linking cross-linking NN 630 631 . . . 632 634 We we PRP 635 647 hypothesized hypothesize VBD 648 652 that that IN 653 657 this this DT 658 667 increased increase VBN 668 673 viral viral JJ 674 687 transcription transcription NN 688 691 was be VBD 692 700 mediated mediate VBN 700 701 , , , 702 704 in in IN 705 709 part part NN 709 710 , , , 711 718 through through IN 719 722 the the DT 723 738 phosphorylation phosphorylation NN 739 741 of of IN 742 746 CREB CREB NNP 746 747 . . . 748 757 Therefore therefore RB 757 758 , , , 759 761 we we PRP 762 774 investigated investigate VBD 775 778 CD2 cd2 NN 779 782 and and CC 783 786 CD3 cd3 NN 787 804 receptor-mediated receptor-mediated JJ 805 815 signalling signalling NN 816 818 in in IN 819 826 primary primary JJ 827 832 human human JJ 833 843 peripheral peripheral JJ 844 849 blood blood NN 850 861 mononuclear mononuclear JJ 862 867 cells cell NNS 868 869 ( ( ( 869 873 PBMC PBMC NNP 873 874 ) ) ) 874 875 . . . 876 879 CD2 cd2 NN 879 880 , , , 881 884 but but CC 885 888 not not RB 889 892 CD3 cd3 NN 892 893 , , , 894 907 cross-linking cross-linking NN 908 917 increased increase VBD 918 922 cAMP camp NN 923 931 detected detect VBN 932 934 by by IN 935 946 competitive competitive JJ 947 960 enzyme-linked enzyme-linked JJ 961 974 immunosorbent immunosorbent JJ 975 980 assay assay NN 981 982 ( ( ( 982 987 ELISA ELISA NNP 987 988 ) ) ) 989 1002 approximately approximately RB 1003 1011 fourfold fourfold RB 1011 1012 . . . 1013 1016 CD2 cd2 NN 1017 1030 cross-linking cross-linking NN 1031 1043 concurrently concurrently RB 1044 1053 increased increase VBD 1054 1069 phosphorylation phosphorylation NN 1070 1072 of of IN 1073 1077 CREB CREB NNP 1078 1086 detected detect VBN 1087 1089 by by IN 1090 1100 immunoblot immunoblot NN 1101 1106 assay assay NN 1107 1116 eightfold eightfold RB 1116 1117 . . . 1118 1128 Consistent consistent JJ 1129 1133 with with IN 1134 1152 post-translational post-translational JJ 1153 1163 regulation regulation NN 1163 1164 , , , 1165 1167 no no DT 1168 1174 change change NN 1175 1177 in in IN 1178 1183 total total JJ 1184 1189 level level NN 1190 1192 of of IN 1193 1197 CREB CREB NNP 1198 1205 protein protein NN 1206 1209 was be VBD 1210 1218 observed observe VBN 1218 1219 . . . 1220 1235 Phosphorylation phosphorylation NN 1236 1238 of of IN 1239 1243 CREB CREB NNP 1244 1252 occurred occur VBD 1253 1260 through through IN 1261 1262 a a DT 1263 1273 herbimycin herbimycin NN 1274 1275 A a NN 1276 1279 and and CC 1280 1288 Rp-cAMP- rp-camp- NN 1289 1298 sensitive sensitive JJ 1299 1306 pathway pathway NN 1306 1307 , , , 1308 1318 suggesting suggest VBG 1319 1334 phosphorylation phosphorylation NN 1335 1343 required require VBD 1344 1354 antecedent antecedent JJ 1355 1365 activation activation NN 1366 1368 of of IN 1369 1373 both both CC 1374 1381 protein protein NN 1382 1390 tyrosine tyrosine NN 1391 1398 kinases kinase NNS 1399 1400 ( ( ( 1400 1403 PTK PTK NNP 1403 1404 ) ) ) 1405 1408 and and CC 1409 1416 protein protein NN 1417 1423 kinase kinase NNP 1424 1425 A A NNP 1426 1427 ( ( ( 1427 1430 PKA PKA NNP 1430 1431 ) ) ) 1431 1432 . . . 1433 1437 Both both CC 1438 1441 CD2 cd2 NN 1442 1445 and and CC 1446 1449 CD3 cd3 NN 1450 1463 cross-linking cross-linking NN 1464 1473 increased increase VBD 1474 1481 binding binding NN 1482 1484 of of IN 1485 1492 nuclear nuclear JJ 1493 1501 proteins protein NNS 1502 1504 to to TO 1505 1506 a a DT 1507 1520 radiolabelled radiolabelle VBN 1521 1524 CRE cre NN 1525 1540 oligonucleotide oligonucleotide NN 1541 1546 probe probe NN 1547 1549 in in IN 1550 1565 electrophoretic electrophoretic JJ 1566 1574 mobility mobility NN 1575 1580 shift shift NN 1581 1587 assays assay NNS 1588 1598 suggesting suggest VBG 1599 1603 that that IN 1604 1614 lymphocyte lymphocyte NN 1615 1625 activation activation NN 1626 1634 enhances enhance VBZ 1635 1642 binding binding NN 1643 1656 independently independently RB 1657 1659 of of IN 1660 1675 phosphorylation phosphorylation NN 1676 1678 of of IN 1679 1683 CREB CREB NNP 1684 1686 at at IN 1687 1693 serine serine NN 1694 1697 133 133 CD 1697 1698 . . . 1699 1704 These these DT 1705 1709 data datum NNS 1710 1718 indicate indicate VBP 1719 1727 specific specific JJ 1728 1738 modulation modulation NN 1739 1741 of of IN 1742 1745 the the DT 1746 1756 CREB/ATF-1 creb/atf-1 NN 1757 1763 family family NN 1764 1766 of of IN 1767 1780 transcription transcription NN 1781 1788 factors factor NNS 1789 1791 by by IN 1792 1795 the the DT 1796 1799 CD2 cd2 NN 1800 1810 signalling signalling NN 1811 1818 pathway pathway NN 1819 1822 and and CC 1823 1830 suggest suggest VBP 1831 1834 CD2 cd2 NN 1835 1843 receptor receptor NN 1844 1854 modulation modulation NN 1855 1857 of of IN 1858 1870 CRE-mediated cre-mediated JJ 1871 1884 transcription transcription NN 1885 1894 following follow VBG 1895 1901 ligand ligand NN 1902 1912 engagement engagement NN 1913 1914 ( ( ( 1914 1918 e.g. e.g. FW 1919 1931 cell-to-cell cell-to-cell JJ 1932 1939 contact contact NN 1939 1940 ) ) ) 1940 1941 . . .