0 15 Transcriptional transcriptional JJ 16 26 regulation regulation NN 27 29 of of IN 30 33 the the DT 34 45 beta-casein beta-casein NN 46 50 gene gene NN 51 53 by by IN 54 63 cytokines cytokine NNS 63 64 : : : 65 75 cross-talk cross-talk NN 76 83 between between IN 84 89 STAT5 STAT5 NNP 90 93 and and CC 94 99 other other JJ 100 109 signaling signal VBG 110 119 molecules molecule NNS 119 120 . . . 122 125 The the DT 126 137 beta-casein beta-casein NN 138 146 promoter promoter NN 147 150 has have VBZ 151 155 been be VBN 156 162 widely widely RB 163 167 used use VBN 168 170 to to TO 171 178 monitor monitor VB 179 182 the the DT 183 193 activation activation NN 194 196 of of IN 197 201 STAT STAT NNP 202 203 ( ( ( 203 209 signal signal NN 210 220 transducer transducer NN 221 224 and and CC 225 234 activator activator NN 235 237 of of IN 238 253 transcription)5 transcription)5 NN 254 259 since since IN 260 265 STAT5 stat5 NN 266 269 was be VBD 270 280 originally originally RB 281 286 found find VBN 287 289 as as IN 290 291 a a DT 292 300 mediator mediator NN 301 303 of of IN 304 317 PRL-inducible prl-inducible JJ 318 329 beta-casein beta-casein NN 330 340 expression expression NN 340 341 . . . 342 349 However however RB 349 350 , , , 351 354 not not RB 355 359 only only RB 360 362 is be VBZ 363 373 expression expression NN 374 376 of of IN 377 380 the the DT 381 392 beta-casein beta-casein NN 393 397 gene gene NN 398 407 regulated regulate VBN 408 410 by by IN 411 416 STAT5 STAT5 NNP 417 420 but but CC 421 423 it it PRP 424 426 is be VBZ 427 431 also also RB 432 440 affected affect VBN 441 443 by by IN 444 449 other other JJ 450 459 molecules molecule NNS 460 464 such such JJ 465 467 as as IN 468 482 glucocorticoid glucocorticoid NN 483 486 and and CC 487 490 Ras Ras NNP 490 491 . . . 492 494 In in IN 495 499 this this DT 500 506 report report NN 506 507 , , , 508 510 we we PRP 511 519 describe describe VBP 520 523 the the DT 524 539 transcriptional transcriptional JJ 540 550 regulation regulation NN 551 553 of of IN 554 557 the the DT 558 569 beta-casein beta-casein NN 570 574 gene gene NN 575 577 by by IN 578 587 cytokines cytokine NNS 588 590 in in IN 591 592 T t NN 593 598 cells cell NNS 598 599 . . . 600 602 We we PRP 603 607 have have VBP 608 613 found find VBN 614 618 that that IN 619 622 the the DT 623 634 beta-casein beta-casein NN 635 639 gene gene NN 640 642 is be VBZ 643 652 expressed express VBN 653 655 in in IN 656 657 a a DT 658 667 cytotoxic cytotoxic JJ 668 669 T t NN 670 674 cell cell NN 675 679 line line NN 679 680 , , , 681 687 CTLL-2 CTLL-2 NNP 687 688 , , , 689 691 in in IN 692 700 response response NN 701 703 to to TO 704 717 interleukin-2 interleukin-2 NN 718 719 ( ( ( 719 723 IL-2 il-2 NN 723 724 ) ) ) 724 725 , , , 726 731 which which WDT 732 741 activates activate VBZ 742 747 STAT5 stat5 NN 747 748 . . . 749 754 While while IN 755 759 IL-4 il-4 NN 760 764 does do VBZ 765 768 not not RB 769 777 activate activate VB 778 783 STAT5 stat5 NN 783 784 , , , 785 787 it it PRP 788 795 induces induce VBZ 796 806 expression expression NN 807 809 of of IN 810 825 STAT5-regulated stat5-regulated JJ 826 831 genes gene NNS 832 834 in in IN 835 841 CTLL-2 ctll-2 NN 841 842 , , , 843 847 i.e. i.e. FW 848 859 beta-casein beta-casein NN 859 860 , , , 861 862 a a DT 863 881 cytokine-inducible cytokine-inducible JJ 882 896 SH2-containing sh2-containing JJ 897 904 protein protein NN 905 906 ( ( ( 906 909 CIS CIS NNP 909 910 ) ) ) 910 911 , , , 912 915 and and CC 916 926 oncostatin oncostatin NN 927 928 M M NNP 929 930 ( ( ( 930 933 OSM OSM NNP 933 934 ) ) ) 934 935 , , , 936 946 suggesting suggest VBG 947 951 that that IN 952 957 STAT6 stat6 NN 958 967 activated activate VBN 968 970 by by IN 971 975 IL-4 il-4 NN 976 987 substitutes substitute NNS 988 991 for for IN 992 995 the the DT 996 1004 function function NN 1005 1007 of of IN 1008 1013 STAT5 stat5 NN 1014 1016 in in IN 1017 1018 T t NN 1019 1024 cells cell NNS 1024 1025 . . . 1026 1038 IL-2-induced il-2-induced JJ 1039 1050 beta-casein beta-casein NN 1051 1061 expression expression NN 1062 1065 was be VBD 1066 1074 enhanced enhance VBN 1075 1077 by by IN 1078 1091 dexamethasone dexamethasone NN 1091 1092 , , , 1093 1096 and and CC 1097 1101 this this DT 1102 1113 synergistic synergistic JJ 1114 1120 effect effect NN 1121 1123 of of IN 1124 1137 Dexamethasone Dexamethasone NNP 1138 1146 requires require VBZ 1147 1150 the the DT 1151 1159 sequence sequence NN 1160 1167 between between IN 1168 1172 -155 -155 CD 1173 1176 and and CC 1177 1181 -193 -193 CD 1182 1184 in in IN 1185 1188 the the DT 1189 1200 beta-casein beta-casein NN 1201 1209 promoter promoter NN 1209 1210 . . . 1211 1225 Coincidentally coincidentally RB 1225 1226 , , , 1227 1228 a a DT 1229 1237 deletion deletion NN 1238 1240 of of IN 1241 1245 this this DT 1246 1252 region region NN 1253 1261 enhanced enhance VBD 1262 1265 the the DT 1266 1278 IL-2-induced il-2-induced JJ 1279 1289 expression expression NN 1290 1292 of of IN 1293 1304 beta-casein beta-casein NN 1304 1305 . . . 1306 1316 Expression expression NN 1317 1319 of of IN 1320 1322 an an DT 1323 1329 active active JJ 1330 1334 form form NN 1335 1337 of of IN 1338 1341 Ras Ras NNP 1341 1342 , , , 1343 1352 Ras(G12V) Ras(G12V) NNP 1352 1353 , , , 1354 1364 suppressed suppress VBD 1365 1368 the the DT 1369 1381 IL-2-induced il-2-induced JJ 1382 1393 beta-casein beta-casein NN 1394 1397 and and CC 1398 1401 OSM osm NN 1402 1406 gene gene NN 1407 1417 expression expression NN 1417 1418 , , , 1419 1422 and and CC 1423 1426 the the DT 1427 1435 negative negative JJ 1436 1442 effect effect NN 1443 1445 of of IN 1446 1449 Ras Ras NNP 1450 1452 is be VBZ 1453 1461 mediated mediate VBN 1462 1464 by by IN 1465 1468 the the DT 1469 1475 region region NN 1476 1483 between between IN 1484 1488 -105 -105 CD 1489 1492 and and CC 1493 1497 -193 -193 CD 1498 1500 in in IN 1501 1504 the the DT 1505 1516 beta-casein beta-casein NN 1517 1525 promoter promoter NN 1525 1526 . . . 1527 1529 In in IN 1530 1538 apparent apparent JJ 1539 1552 contradiction contradiction NN 1552 1553 , , , 1554 1564 expression expression NN 1565 1567 of of IN 1568 1569 a a DT 1570 1578 dominant dominant JJ 1579 1587 negative negative JJ 1588 1592 form form NN 1593 1595 of of IN 1596 1599 Ras Ras NNP 1599 1600 , , , 1601 1607 RasN17 RasN17 NNP 1607 1608 , , , 1609 1613 also also RB 1614 1623 inhibited inhibit VBD 1624 1636 IL-2-induced il-2-induced JJ 1637 1647 activation activation NN 1648 1650 of of IN 1651 1654 the the DT 1655 1663 promoter promoter NN 1664 1674 containing contain VBG 1675 1678 the the DT 1679 1686 minimal minimal JJ 1687 1698 beta-casein beta-casein NN 1699 1704 STAT5 stat5 NN 1705 1712 element element NN 1713 1715 as as RB 1716 1720 well well RB 1721 1723 as as IN 1724 1727 the the DT 1728 1737 promoters promoter NNS 1738 1740 of of IN 1741 1744 CIS CIS NNP 1745 1748 and and CC 1749 1752 OSM OSM NNP 1752 1753 . . . 1754 1756 In in IN 1757 1765 addition addition NN 1765 1766 , , , 1767 1776 Ras(G12V) ras(g12v) NN 1777 1789 complemented complement VBD 1790 1799 signaling signaling NN 1800 1802 by by IN 1803 1805 an an DT 1806 1820 erythropoietin erythropoietin NN 1821 1829 receptor receptor NN 1830 1836 mutant mutant NN 1837 1846 defective defective JJ 1847 1849 in in IN 1850 1853 Ras Ras NNP 1854 1864 activation activation NN 1865 1868 and and CC 1869 1878 augmented augment VBD 1879 1882 the the DT 1883 1893 activation activation NN 1894 1896 of of IN 1897 1900 the the DT 1901 1912 beta-casein beta-casein NN 1913 1921 promoter promoter NN 1922 1924 by by IN 1925 1928 the the DT 1929 1935 mutant mutant JJ 1936 1950 erythropoietin erythropoietin NN 1951 1959 receptor receptor NN 1960 1969 signaling signaling NN 1969 1970 , , , 1971 1981 suggesting suggest VBG 1982 1983 a a DT 1984 1992 possible possible JJ 1993 1997 role role NN 1998 2000 of of IN 2001 2004 Ras Ras NNP 2005 2007 in in IN 2008 2022 Stat5-mediated stat5-mediated JJ 2023 2027 gene gene NN 2028 2038 expression expression NN 2038 2039 . . . 2040 2045 These these DT 2046 2053 results result NNS 2054 2066 collectively collectively RB 2067 2073 reveal reveal VBP 2074 2075 a a DT 2076 2083 complex complex JJ 2084 2095 interaction interaction NN 2096 2098 of of IN 2099 2104 STAT5 stat5 NN 2105 2109 with with IN 2110 2115 other other JJ 2116 2125 signaling signaling NN 2126 2134 pathways pathway NNS 2135 2138 and and CC 2139 2149 illustrate illustrate VBP 2150 2154 that that IN 2155 2165 regulation regulation NN 2166 2168 of of IN 2169 2173 gene gene NN 2174 2184 expression expression NN 2185 2193 requires require VBZ 2194 2205 integration integration NN 2206 2208 of of IN 2209 2217 opposing opposing JJ 2218 2225 signals signal NNS 2225 2226 . . .