0 10 Regulation Regulation NNP 11 13 of of IN 14 19 M-CSF M-CSF NNP 20 30 expression expression NN 31 33 by by IN 34 39 M-CSF M-CSF NNP 39 40 : : : 41 45 role role NN 46 48 of of IN 49 56 protein protein NN 57 63 kinase kinase NNP 64 65 C C NNP 66 69 and and CC 70 83 transcription transcription NN 84 90 factor factor NN 91 93 NF NF NNP 94 99 kappa kappa NN 100 102 B. B. NNP 104 133 Macrophage-colony-stimulating macrophage-colony-stimulating JJ 134 140 factor factor NN 141 142 ( ( ( 142 147 M-CSF M-CSF NNP 147 148 ) ) ) 148 149 , , , 150 154 also also RB 155 163 referred refer VBN 164 166 to to TO 167 169 as as IN 170 175 CSF-1 csf-1 NN 175 176 , , , 177 186 regulates regulate VBZ 187 190 the the DT 191 199 survival survival NN 199 200 , , , 201 207 growth growth NN 207 208 , , , 209 224 differentiation differentiation NN 225 228 and and CC 229 239 functional functional JJ 240 248 activity activity NN 249 251 of of IN 252 261 monocytes monocyte NNS 262 264 by by IN 265 272 binding bind VBG 273 275 to to TO 276 277 a a DT 278 284 single single JJ 285 290 class class NN 291 293 of of IN 294 307 high-affinity high-affinity JJ 308 312 cell cell NN 313 320 surface surface NN 321 330 receptors receptor NNS 330 331 , , , 332 337 known know VBN 338 340 to to TO 341 343 be be VB 344 347 the the DT 348 355 product product NN 356 358 of of IN 359 362 the the DT 363 368 c-fms c-fms NN 369 382 protooncogene protooncogene NN 382 383 . . . 384 387 The the DT 388 397 detection detection NN 398 400 of of IN 401 405 both both CC 406 411 M-CSF M-CSF NNP 412 415 and and CC 416 421 c-fms c-fms NN 422 432 expression expression NN 433 435 by by IN 436 441 cells cell NNS 442 444 of of IN 445 448 the the DT 449 457 monocyte monocyte NN 458 465 lineage lineage NN 466 469 has have VBZ 470 479 suggested suggest VBN 480 484 that that IN 485 490 M-CSF M-CSF NNP 491 494 may may MD 495 498 act act VB 499 501 by by IN 502 504 an an DT 505 514 autocrine autocrine JJ 515 524 mechanism mechanism NN 524 525 . . . 526 539 Interestingly interestingly RB 539 540 , , , 541 543 it it PRP 544 547 has have VBZ 548 552 been be VBN 553 558 shown show VBN 559 563 that that IN 564 569 M-CSF M-CSF NNP 570 573 can can MD 574 580 induce induce VB 581 584 the the DT 585 595 expression expression NN 596 598 of of IN 599 602 its its PRP$ 603 606 own own JJ 607 611 gene gene NN 611 612 . . . 613 621 Although although IN 622 633 sensitivity sensitivity NN 634 636 to to TO 637 642 M-CSF M-CSF NNP 643 646 can can MD 647 649 be be VB 650 659 modulated modulate VBN 660 662 by by IN 663 673 regulation regulation NN 674 676 of of IN 677 685 receptor receptor NN 686 696 expression expression NN 697 700 and and CC 701 709 function function NN 709 710 , , , 711 716 M-CSF M-CSF NNP 717 731 responsiveness responsiveness NN 732 734 is be VBZ 735 742 largely largely RB 743 753 determined determine VBN 754 756 at at IN 757 758 a a DT 759 771 postreceptor postreceptor NN 772 777 level level NN 777 778 . . . 779 781 To to TO 782 786 date date NN 786 787 , , , 788 794 little little JJ 795 797 is be VBZ 798 803 known know VBN 804 809 about about IN 810 813 the the DT 814 827 intracellular intracellular JJ 828 835 pathway pathway NN 836 838 of of IN 839 844 M-CSF M-CSF NNP 845 851 signal signal NN 852 864 transduction transduction NN 864 865 . . . 866 868 We we PRP 869 873 have have VBP 874 883 therefore therefore RB 884 896 investigated investigate VBN 897 900 the the DT 901 908 changes change NNS 909 911 in in IN 912 919 protein protein NN 920 926 kinase kinase NNP 927 928 C C NNP 929 930 ( ( ( 930 933 PKC PKC NNP 933 934 ) ) ) 935 943 activity activity NN 944 948 upon upon IN 949 957 exposure exposure NN 958 960 of of IN 961 970 monocytes monocyte NNS 971 973 to to TO 974 979 M-CSF M-CSF NNP 979 980 . . . 981 983 We we PRP 984 988 show show VBP 989 993 that that IN 994 999 M-CSF M-CSF NNP 1000 1009 activates activate VBZ 1010 1013 and and CC 1014 1026 translocates translocate VBZ 1027 1030 PKC PKC NNP 1030 1031 . . . 1032 1042 Inhibition Inhibition NNP 1043 1045 of of IN 1046 1049 PKC PKC NNP 1050 1052 by by IN 1053 1056 the the DT 1057 1069 isoquinoline isoquinoline NN 1070 1080 derivative derivative JJ 1081 1083 H7 h7 NN 1084 1093 abolishes abolish VBZ 1094 1103 induction induction NN 1104 1106 of of IN 1107 1112 M-CSF M-CSF NNP 1113 1115 by by IN 1116 1121 M-CSF M-CSF NNP 1121 1122 . . . 1123 1134 Furthermore furthermore RB 1134 1135 , , , 1136 1146 activation activation NN 1147 1149 of of IN 1150 1153 PKC PKC NNP 1154 1157 was be VBD 1158 1183 pertussis-toxin-sensitive pertussis-toxin-sensitive JJ 1184 1187 and and CC 1188 1191 was be VBD 1192 1202 associated associate VBN 1203 1207 with with IN 1208 1211 the the DT 1212 1221 detection detection NN 1222 1224 of of IN 1225 1227 an an DT 1228 1230 NF NF NNP 1231 1236 kappa kappa NN 1237 1238 B B NNP 1239 1246 protein protein NN 1247 1249 in in IN 1250 1257 nuclear nuclear JJ 1258 1266 extracts extract NNS 1267 1269 of of IN 1270 1283 M-CSF-induced m-csf-induced JJ 1284 1289 blood blood NN 1290 1299 monocytes monocyte NNS 1300 1303 but but CC 1304 1307 not not RB 1308 1310 in in IN 1311 1320 monocytes monocyte NNS 1321 1328 exposed expose VBN 1329 1331 to to TO 1332 1338 medium medium NN 1339 1348 treatment treatment NN 1349 1353 only only RB 1353 1354 . . . 1355 1358 The the DT 1359 1366 results result NNS 1367 1374 suggest suggest VBP 1375 1379 that that IN 1380 1385 M-CSF M-CSF NNP 1386 1395 induction induction NN 1396 1398 of of IN 1399 1404 M-CSF M-CSF NNP 1405 1413 involves involve VBZ 1414 1415 G G NNP 1416 1424 proteins protein NNS 1424 1425 , , , 1426 1429 PKC PKC NNP 1430 1433 and and CC 1434 1436 NF NF NNP 1437 1442 kappa kappa NN 1443 1444 B B NNP 1444 1445 . . .