0 7 Phorbol Phorbol NNP 8 21 ester-induced ester-induced JJ 22 33 mononuclear mononuclear JJ 34 38 cell cell NN 39 54 differentiation differentiation NN 55 57 is be VBZ 58 65 blocked block VBN 66 68 by by IN 69 72 the the DT 73 90 mitogen-activated mitogen-activated JJ 91 98 protein protein NN 99 105 kinase kinase NNP 106 112 kinase kinase NNP 113 114 ( ( ( 114 117 MEK MEK NNP 117 118 ) ) ) 119 128 inhibitor inhibitor NN 129 136 PD98059 pd98059 NN 136 137 . . . 139 142 The the DT 143 150 purpose purpose NN 151 153 of of IN 154 158 this this DT 159 164 study study NN 165 168 was be VBD 169 171 to to TO 172 180 evaluate evaluate VB 181 188 whether whether IN 189 192 the the DT 193 210 mitogen-activated mitogen-activated JJ 211 218 protein protein NN 219 225 kinase kinase NNP 226 227 ( ( ( 227 231 MAPK MAPK NNP 231 232 ) ) ) 233 242 signaling signaling NN 243 250 pathway pathway NN 251 262 contributes contribute VBZ 263 265 to to TO 266 302 12-O-tetradecanoylphorbol-13-acetate 12-O-tetradecanoylphorbol-13-acetate NNP 303 304 ( ( ( 304 316 TPA)-induced tpa)-induced JJ 317 328 mononuclear mononuclear JJ 329 344 differentiation differentiation NN 345 347 in in IN 348 351 the the DT 352 357 human human JJ 358 370 myeloblastic myeloblastic JJ 371 379 leukemia leukemia NN 380 384 ML-1 ml-1 NN 385 390 cells cell NNS 390 391 . . . 392 396 Upon upon IN 397 400 TPA TPA NNP 401 410 treatment treatment NN 410 411 , , , 412 415 the the DT 416 424 activity activity NN 425 427 of of IN 428 432 ERK1 ERK1 NNP 433 436 and and CC 437 441 ERK2 ERK2 NNP 442 449 rapidly rapidly RB 450 459 increased increase VBD 459 460 , , , 461 465 with with IN 466 473 maximal maximal JJ 474 483 induction induction NN 484 491 between between IN 492 493 1 1 CD 494 497 and and CC 498 499 3 3 CD 500 501 h h NN 501 502 , , , 503 508 while while IN 509 513 ERK2 erk2 NN 514 521 protein protein NN 522 528 levels level NNS 529 537 remained remain VBD 538 546 constant constant JJ 546 547 . . . 548 551 The the DT 552 560 activity activity NN 561 563 of of IN 564 568 JNK1 JNK1 NNP 569 572 was be VBD 573 577 also also RB 578 591 significantly significantly RB 592 599 induced induce VBN 599 600 , , , 601 605 with with IN 606 610 JNK1 jnk1 NN 611 618 protein protein NN 619 625 levels level NNS 626 636 increasing increase VBG 637 647 moderately moderately RB 648 654 during during IN 655 663 exposure exposure NN 664 666 to to TO 667 670 TPA TPA NNP 670 671 . . . 672 681 Treatment Treatment NNP 682 684 of of IN 685 690 cells cell NNS 691 695 with with IN 696 703 PD98059 PD98059 NNP 703 704 , , , 705 706 a a DT 707 715 specific specific JJ 716 725 inhibitor inhibitor NN 726 728 of of IN 729 746 mitogen-activated mitogen-activated JJ 747 754 protein protein NN 755 761 kinase kinase NNP 762 768 kinase kinase NNP 769 770 ( ( ( 770 773 MEK MEK NNP 773 774 ) ) ) 774 775 , , , 776 785 inhibited inhibit VBD 786 797 TPA-induced tpa-induced JJ 798 802 ERK2 erk2 NN 803 811 activity activity NN 811 812 . . . 813 824 Furthermore furthermore RB 824 825 , , , 826 833 PD98059 PD98059 NNP 834 844 completely completely RB 845 852 blocked block VBD 853 856 the the DT 857 868 TPA-induced tpa-induced JJ 869 884 differentiation differentiation NN 885 887 of of IN 888 892 ML-1 ml-1 NN 893 898 cells cell NNS 898 899 , , , 900 902 as as IN 903 911 assessed assess VBN 912 914 by by IN 915 916 a a DT 917 923 number number NN 924 926 of of IN 927 935 features feature NNS 936 946 associated associate VBN 947 951 with with IN 952 963 mononuclear mononuclear JJ 964 979 differentiation differentiation NN 980 989 including include VBG 990 997 changes change NNS 998 1000 in in IN 1001 1011 morphology morphology NN 1011 1012 , , , 1013 1024 nonspecific nonspecific JJ 1025 1033 esterase esterase NN 1034 1042 activity activity NN 1042 1043 , , , 1044 1054 phagocytic phagocytic JJ 1055 1062 ability ability NN 1062 1063 , , , 1064 1069 NADPH NADPH NNP 1070 1077 oxidase oxidase NN 1078 1086 activity activity NN 1086 1087 , , , 1088 1101 mitochondrial mitochondrial JJ 1102 1113 respiration respiration NN 1113 1114 , , , 1115 1118 and and CC 1119 1124 c-jun c-jun NN 1125 1129 mRNA mrna NN 1130 1142 inducibility inducibility NN 1142 1143 . . . 1144 1146 We we PRP 1147 1155 conclude conclude VBP 1156 1160 that that IN 1161 1171 activation activation NN 1172 1174 of of IN 1175 1178 the the DT 1179 1186 MEK/ERK MEK/ERK NNP 1187 1196 signaling signaling NN 1197 1204 pathway pathway NN 1205 1207 is be VBZ 1208 1217 necessary necessary JJ 1218 1221 for for IN 1222 1233 TPA-induced tpa-induced JJ 1234 1245 mononuclear mononuclear JJ 1246 1250 cell cell NN 1251 1266 differentiation differentiation NN 1266 1267 . . .