0 10 Activation Activation NNP 11 13 of of IN 14 19 STAT5 stat5 NN 20 22 by by IN 23 27 IL-4 il-4 NN 28 34 relies rely VBZ 35 37 on on IN 38 43 Janus Janus NNP 44 50 kinase kinase NNP 51 59 function function NN 60 63 but but CC 64 67 not not RB 68 70 on on IN 71 79 receptor receptor NN 80 88 tyrosine tyrosine NN 89 104 phosphorylation phosphorylation NN 104 105 , , , 106 109 and and CC 110 113 can can MD 114 124 contribute contribute VB 125 127 to to TO 128 132 both both DT 133 137 cell cell NN 138 151 proliferation proliferation NN 152 155 and and CC 156 160 gene gene NN 161 171 regulation regulation NN 171 172 . . . 174 176 We we PRP 177 181 have have VBP 182 194 investigated investigate VBN 195 205 mechanisms mechanism NNS 206 209 and and CC 210 222 consequences consequence NNS 223 225 of of IN 226 231 STAT5 stat5 NN 232 242 activation activation NN 243 250 through through IN 251 254 the the DT 255 260 human human JJ 261 265 IL-4 il-4 NN 266 274 receptor receptor NN 275 276 ( ( ( 276 281 IL-4R IL-4R NNP 281 282 ) ) ) 282 283 . . . 284 286 By by IN 287 299 functionally functionally RB 300 310 expressing express VBG 311 319 receptor receptor NN 320 327 mutants mutant NNS 328 330 in in IN 331 334 the the DT 335 341 murine murine JJ 342 347 pro-B pro-b JJ 348 352 cell cell NN 353 357 line line NN 358 363 Ba/F3 ba/f3 NN 363 364 , , , 365 367 we we PRP 368 373 could could MD 374 378 show show VB 379 383 that that IN 384 398 phosphorylated phosphorylate VBN 399 407 tyrosine tyrosine NN 408 416 residues residue NNS 417 423 within within IN 424 427 the the DT 428 433 IL-4R IL-4R NNP 434 439 alpha alpha NN 440 445 chain chain NN 446 449 are be VBP 450 461 dispensable dispensable JJ 462 465 for for IN 466 478 IL-4-induced il-4-induced JJ 479 484 STAT5 STAT5 NNP 485 493 activity activity NN 493 494 . . . 495 502 However however RB 502 503 , , , 504 514 disruption disruption NN 515 517 of of IN 518 519 a a DT 520 537 membrane-proximal membrane-proximal JJ 538 550 proline-rich proline-rich JJ 551 559 sequence sequence NN 560 565 motif motif NN 566 567 ( ( ( 567 568 ‘ ` `` 568 572 box1 box1 NN 572 573 ’ ' '' 573 574 ) ) ) 575 577 in in IN 578 584 either either CC 585 592 subunit subunit NN 593 595 of of IN 596 599 the the DT 600 609 bipartite bipartite JJ 610 615 IL-4R il-4r NN 616 625 abolished abolish VBD 626 629 not not RB 630 634 only only RB 635 649 ligand-induced ligand-induced JJ 650 658 tyrosine tyrosine NN 659 674 phosphorylation phosphorylation NN 675 677 of of IN 678 683 Janus Janus NNP 684 691 kinases kinase NNS 692 696 JAK1 jak1 NN 697 700 and and CC 701 705 JAK3 JAK3 NNP 705 706 , , , 707 710 but but CC 711 715 also also RB 716 730 IL-4-triggered il-4-triggered JJ 731 741 activation activation NN 742 744 of of IN 745 750 STAT5 STAT5 NNP 751 754 and and CC 755 766 concomitant concomitant JJ 767 771 cell cell NN 772 785 proliferation proliferation NN 785 786 . . . 787 788 A a DT 789 806 dominant-negative dominant-negative JJ 807 814 version version NN 815 817 of of IN 818 824 STAT5b STAT5b NNP 824 825 , , , 826 829 but but CC 830 833 not not RB 834 836 of of IN 837 843 STAT5a STAT5a NNP 843 844 , , , 845 855 interfered interfere VBD 856 860 with with IN 861 873 IL-4-induced il-4-induced JJ 874 877 DNA DNA NNP 878 887 synthesis synthesis NN 888 890 in in IN 891 896 Ba/F3 ba/f3 NN 897 902 cells cell NNS 902 903 , , , 904 914 suggesting suggest VBG 915 917 an an DT 918 929 involvement involvement NN 930 932 of of IN 933 939 STAT5b STAT5b NNP 940 942 in in IN 943 946 the the DT 947 954 control control NN 955 957 of of IN 958 962 cell cell NN 963 976 proliferation proliferation NN 977 984 through through IN 985 991 IL-4R. IL-4R. NNP 992 1000 Reporter Reporter NNP 1001 1005 gene gene NN 1006 1017 experiments experiment NNS 1018 1025 finally finally RB 1026 1032 showed show VBD 1033 1037 that that IN 1038 1051 transcription transcription NN 1052 1056 from from IN 1057 1066 promoters promoter NNS 1067 1069 of of IN 1070 1075 STAT5 STAT5 NNP 1076 1082 target target NN 1083 1088 genes gene NNS 1089 1092 can can MD 1093 1095 be be VB 1096 1108 specifically specifically RB 1109 1116 induced induce VBN 1117 1119 by by IN 1120 1131 challenging challenge VBG 1132 1137 cells cell NNS 1138 1142 with with IN 1143 1147 IL-4 il-4 NN 1147 1148 , , , 1149 1152 and and CC 1153 1157 that that IN 1158 1162 both both CC 1163 1169 STAT5a STAT5a NNP 1170 1173 and and CC 1174 1180 STAT5b STAT5b NNP 1181 1184 can can MD 1185 1195 contribute contribute VB 1196 1198 to to TO 1199 1213 IL-4-triggered il-4-triggered JJ 1214 1229 transcriptional transcriptional JJ 1230 1237 control control NN 1237 1238 . . .