Differential expression and regulation of the c-src and c-fgr protooncogenes in myelomonocytic cells.
To study the expression of src-related protooncogenes during the development of myeloid cells and the regulation of these genes by the colony-stimulating factors that control myelopoiesis, normal monocytic cells at distinct stages of differentiation were derived from murine bone marrow with the monocytic lineage colony-stimulating factor CSF-1. Protooncogene expression was also examined in uncultured human myeloid leukemia cells. While c-src transcripts were detected in myeloid leukemia cells representative of all stages of differentiation, the highly related gene c-fgr was expressed at high levels only at later developmental stages, both in normal cells committed to the monocytic lineage and in leukemic cells with a differentiated myelomonocytic phenotype. When bone marrow-derived monocytic cells were synchronized and stimulated to proliferate with CSF-1, c-fgr transcripts (but not transcripts from the highly related genes c-src or c-yes) were induced 8 hr after the addition of CSF-1 and decreased to low levels by 20 hr as the monocytic cells entered S phase. The selective induction of c-fgr mRNA by CSF-1 suggests that this tyrosine kinase may have a unique function in normal monocytic cells, distinct from other src-related tyrosine kinases.
D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D003115:Colony-Stimulating Factors / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D006410:Hematopoiesis / Q000187:drug effects; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D007951:Leukemia, Myeloid / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008809:Mice, Inbred C3H; D009000:Monocytes / Q000166:cytology; D011505:Protein-Tyrosine Kinases / Q000096:biosynthesis / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis* / Q000235:genetics; D016392:Proto-Oncogene Proteins pp60(c-src); D011519:Proto-Oncogenes; D012333:RNA, Messenger / Q000032:analysis; D019061:src-Family Kinases
D003115:Colony-Stimulating Factors; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D011505:Protein-Tyrosine Kinases; D016392:Proto-Oncogene Proteins pp60(c-src); C053102:proto-oncogene proteins c-fgr; D019061:src-Family Kinases