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. 1987 Jul;84(13):4480–4484. doi: 10.1073/pnas.84.13.4480

Differential expression and regulation of the c-src and c-fgr protooncogenes in myelomonocytic cells.

C L Willman, C C Stewart, J K Griffith, S J Stewart, T B Tomasi
PMCID: PMC305113  PMID: 2440024

Abstract

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.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Boettiger D., Anderson S., Dexter T. M. Effect of src infection on long-term marrow cultures: increased self-renewal of hemopoietic progenitor cells without leukemia. Cell. 1984 Mar;36(3):763–773. doi: 10.1016/0092-8674(84)90356-8. [DOI] [PubMed] [Google Scholar]
  2. Bolen J. B., Thiele C. J., Israel M. A., Yonemoto W., Lipsich L. A., Brugge J. S. Enhancement of cellular src gene product associated tyrosyl kinase activity following polyoma virus infection and transformation. Cell. 1984 Oct;38(3):767–777. doi: 10.1016/0092-8674(84)90272-1. [DOI] [PubMed] [Google Scholar]
  3. Brugge J. S., Cotton P. C., Queral A. E., Barrett J. N., Nonner D., Keane R. W. Neurones express high levels of a structurally modified, activated form of pp60c-src. Nature. 1985 Aug 8;316(6028):554–557. doi: 10.1038/316554a0. [DOI] [PubMed] [Google Scholar]
  4. Carmier J. F., Samarut J. Chicken myeloid stem cells infected by retroviruses carrying the v-fps oncogene do not require exogenous growth factors to differentiate in vitro. Cell. 1986 Jan 17;44(1):159–165. doi: 10.1016/0092-8674(86)90494-0. [DOI] [PubMed] [Google Scholar]
  5. Chirgwin J. M., Przybyla A. E., MacDonald R. J., Rutter W. J. Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease. Biochemistry. 1979 Nov 27;18(24):5294–5299. doi: 10.1021/bi00591a005. [DOI] [PubMed] [Google Scholar]
  6. Civin C. I., Strauss L. C., Brovall C., Fackler M. J., Schwartz J. F., Shaper J. H. Antigenic analysis of hematopoiesis. III. A hematopoietic progenitor cell surface antigen defined by a monoclonal antibody raised against KG-1a cells. J Immunol. 1984 Jul;133(1):157–165. [PubMed] [Google Scholar]
  7. Cochran B. H., Zullo J., Verma I. M., Stiles C. D. Expression of the c-fos gene and of an fos-related gene is stimulated by platelet-derived growth factor. Science. 1984 Nov 30;226(4678):1080–1082. doi: 10.1126/science.6093261. [DOI] [PubMed] [Google Scholar]
  8. Cook W. D., Metcalf D., Nicola N. A., Burgess A. W., Walker F. Malignant transformation of a growth factor-dependent myeloid cell line by Abelson virus without evidence of an autocrine mechanism. Cell. 1985 Jul;41(3):677–683. doi: 10.1016/s0092-8674(85)80048-9. [DOI] [PubMed] [Google Scholar]
  9. Courtneidge S. A., Smith A. E. Polyoma virus transforming protein associates with the product of the c-src cellular gene. Nature. 1983 Jun 2;303(5916):435–439. doi: 10.1038/303435a0. [DOI] [PubMed] [Google Scholar]
  10. Crissman H. A., Darzynkiewicz Z., Tobey R. A., Steinkamp J. A. Normal and perturbed Chinese hamster ovary cells: correlation of DNA, RNA, and protein content by flow cytometry. J Cell Biol. 1985 Jul;101(1):141–147. doi: 10.1083/jcb.101.1.141. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Curran T., Peters G., Van Beveren C., Teich N. M., Verma I. M. FBJ murine osteosarcoma virus: identification and molecular cloning of biologically active proviral DNA. J Virol. 1982 Nov;44(2):674–682. doi: 10.1128/jvi.44.2.674-682.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. DeLorbe W. J., Luciw P. A., Goodman H. M., Varmus H. E., Bishop J. M. Molecular cloning and characterization of avian sarcoma virus circular DNA molecules. J Virol. 1980 Oct;36(1):50–61. doi: 10.1128/jvi.36.1.50-61.1980. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Donner L., Fedele L. A., Garon C. F., Anderson S. J., Sherr C. J. McDonough feline sarcoma virus: characterization of the molecularly cloned provirus and its feline oncogene (v-fms). J Virol. 1982 Feb;41(2):489–500. doi: 10.1128/jvi.41.2.489-500.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Dugaiczyk A., Haron J. A., Stone E. M., Dennison O. E., Rothblum K. N., Schwartz R. J. Cloning and sequencing of a deoxyribonucleic acid copy of glyceraldehyde-3-phosphate dehydrogenase messenger ribonucleic acid isolated from chicken muscle. Biochemistry. 1983 Mar 29;22(7):1605–1613. doi: 10.1021/bi00276a013. [DOI] [PubMed] [Google Scholar]
  15. Gee C. E., Griffin J., Sastre L., Miller L. J., Springer T. A., Piwnica-Worms H., Roberts T. M. Differentiation of myeloid cells is accompanied by increased levels of pp60c-src protein and kinase activity. Proc Natl Acad Sci U S A. 1986 Jul;83(14):5131–5135. doi: 10.1073/pnas.83.14.5131. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Gibbs C. P., Tanaka A., Anderson S. K., Radul J., Baar J., Ridgway A., Kung H. J., Fujita D. J. Isolation and structural mapping of a human c-src gene homologous to the transforming gene (v-src) of Rous sarcoma virus. J Virol. 1985 Jan;53(1):19–24. doi: 10.1128/jvi.53.1.19-24.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Golden A., Nemeth S. P., Brugge J. S. Blood platelets express high levels of the pp60c-src-specific tyrosine kinase activity. Proc Natl Acad Sci U S A. 1986 Feb;83(4):852–856. doi: 10.1073/pnas.83.4.852. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Greaves M. F. Differentiation-linked leukemogenesis in lymphocytes. Science. 1986 Nov 7;234(4777):697–704. doi: 10.1126/science.3535067. [DOI] [PubMed] [Google Scholar]
  19. Griffin J. D., Larcom P., Schlossman S. F. Use of surface markers to identify a subset of acute myelomonocytic leukemia cells with progenitor cell properties. Blood. 1983 Dec;62(6):1300–1303. [PubMed] [Google Scholar]
  20. Griffin J. D., Mayer R. J., Weinstein H. J., Rosenthal D. S., Coral F. S., Beveridge R. P., Schlossman S. F. Surface marker analysis of acute myeloblastic leukemia: identification of differentiation-associated phenotypes. Blood. 1983 Sep;62(3):557–563. [PubMed] [Google Scholar]
  21. Hunter T., Cooper J. A. Protein-tyrosine kinases. Annu Rev Biochem. 1985;54:897–930. doi: 10.1146/annurev.bi.54.070185.004341. [DOI] [PubMed] [Google Scholar]
  22. Kitamura N., Kitamura A., Toyoshima K., Hirayama Y., Yoshida M. Avian sarcoma virus Y73 genome sequence and structural similarity of its transforming gene product to that of Rous sarcoma virus. Nature. 1982 May 20;297(5863):205–208. doi: 10.1038/297205a0. [DOI] [PubMed] [Google Scholar]
  23. Lautenberger J. A., Schulz R. A., Garon C. F., Tsichlis P. N., Papas T. S. Molecular cloning of avian myelocytomatosis virus (MC29) transforming sequences. Proc Natl Acad Sci U S A. 1981 Mar;78(3):1518–1522. doi: 10.1073/pnas.78.3.1518. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Marth J. D., Peet R., Krebs E. G., Perlmutter R. M. A lymphocyte-specific protein-tyrosine kinase gene is rearranged and overexpressed in the murine T cell lymphoma LSTRA. Cell. 1985 Dec;43(2 Pt 1):393–404. doi: 10.1016/0092-8674(85)90169-2. [DOI] [PubMed] [Google Scholar]
  25. Metcalf D. The granulocyte-macrophage colony-stimulating factors. Science. 1985 Jul 5;229(4708):16–22. doi: 10.1126/science.2990035. [DOI] [PubMed] [Google Scholar]
  26. Nishizawa M., Semba K., Yoshida M. C., Yamamoto T., Sasaki M., Toyoshima K. Structure, expression, and chromosomal location of the human c-fgr gene. Mol Cell Biol. 1986 Feb;6(2):511–517. doi: 10.1128/mcb.6.2.511. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Parker R. C., Mardon G., Lebo R. V., Varmus H. E., Bishop J. M. Isolation of duplicated human c-src genes located on chromosomes 1 and 20. Mol Cell Biol. 1985 Apr;5(4):831–838. doi: 10.1128/mcb.5.4.831. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Pierce J. H., Di Fiore P. P., Aaronson S. A., Potter M., Pumphrey J., Scott A., Ihle J. N. Neoplastic transformation of mast cells by Abelson-MuLV: abrogation of IL-3 dependence by a nonautocrine mechanism. Cell. 1985 Jul;41(3):685–693. doi: 10.1016/s0092-8674(85)80049-0. [DOI] [PubMed] [Google Scholar]
  29. Ralston R., Bishop J. M. The product of the protooncogene c-src is modified during the cellular response to platelet-derived growth factor. Proc Natl Acad Sci U S A. 1985 Dec;82(23):7845–7849. doi: 10.1073/pnas.82.23.7845. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Russell P., Nurse P. Schizosaccharomyces pombe and Saccharomyces cerevisiae: a look at yeasts divided. Cell. 1986 Jun 20;45(6):781–782. doi: 10.1016/0092-8674(86)90550-7. [DOI] [PubMed] [Google Scholar]
  31. Sacca R., Stanley E. R., Sherr C. J., Rettenmier C. W. Specific binding of the mononuclear phagocyte colony-stimulating factor CSF-1 to the product of the v-fms oncogene. Proc Natl Acad Sci U S A. 1986 May;83(10):3331–3335. doi: 10.1073/pnas.83.10.3331. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Semba K., Nishizawa M., Miyajima N., Yoshida M. C., Sukegawa J., Yamanashi Y., Sasaki M., Yamamoto T., Toyoshima K. yes-related protooncogene, syn, belongs to the protein-tyrosine kinase family. Proc Natl Acad Sci U S A. 1986 Aug;83(15):5459–5463. doi: 10.1073/pnas.83.15.5459. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Sherr C. J., Rettenmier C. W., Sacca R., Roussel M. F., Look A. T., Stanley E. R. The c-fms proto-oncogene product is related to the receptor for the mononuclear phagocyte growth factor, CSF-1. Cell. 1985 Jul;41(3):665–676. doi: 10.1016/s0092-8674(85)80047-7. [DOI] [PubMed] [Google Scholar]
  34. Simon M. A., Drees B., Kornberg T., Bishop J. M. The nucleotide sequence and the tissue-specific expression of Drosophila c-src. Cell. 1985 Oct;42(3):831–840. doi: 10.1016/0092-8674(85)90279-x. [DOI] [PubMed] [Google Scholar]
  35. Sorge L. K., Levy B. T., Maness P. F. pp60c-src is developmentally regulated in the neural retina. Cell. 1984 Feb;36(2):249–257. doi: 10.1016/0092-8674(84)90218-6. [DOI] [PubMed] [Google Scholar]
  36. Thomas P. S. Hybridization of denatured RNA and small DNA fragments transferred to nitrocellulose. Proc Natl Acad Sci U S A. 1980 Sep;77(9):5201–5205. doi: 10.1073/pnas.77.9.5201. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Thompson C. B., Challoner P. B., Neiman P. E., Groudine M. Levels of c-myc oncogene mRNA are invariant throughout the cell cycle. 1985 Mar 28-Apr 3Nature. 314(6009):363–366. doi: 10.1038/314363a0. [DOI] [PubMed] [Google Scholar]
  38. Tronick S. R., Popescu N. C., Cheah M. S., Swan D. C., Amsbaugh S. C., Lengel C. R., DiPaolo J. A., Robbins K. C. Isolation and chromosomal localization of the human fgr protooncogene, a distinct member of the tyrosine kinase gene family. Proc Natl Acad Sci U S A. 1985 Oct;82(19):6595–6599. doi: 10.1073/pnas.82.19.6595. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Tushinski R. J., Oliver I. T., Guilbert L. J., Tynan P. W., Warner J. R., Stanley E. R. Survival of mononuclear phagocytes depends on a lineage-specific growth factor that the differentiated cells selectively destroy. Cell. 1982 Jan;28(1):71–81. doi: 10.1016/0092-8674(82)90376-2. [DOI] [PubMed] [Google Scholar]
  40. Tushinski R. J., Stanley E. R. The regulation of mononuclear phagocyte entry into S phase by the colony stimulating factor CSF-1. J Cell Physiol. 1985 Feb;122(2):221–228. doi: 10.1002/jcp.1041220210. [DOI] [PubMed] [Google Scholar]
  41. Wahl G. M., Stern M., Stark G. R. Efficient transfer of large DNA fragments from agarose gels to diazobenzyloxymethyl-paper and rapid hybridization by using dextran sulfate. Proc Natl Acad Sci U S A. 1979 Aug;76(8):3683–3687. doi: 10.1073/pnas.76.8.3683. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Walker E. B., Akporiaye E. T., Warner N. L., Stewart C. C. Characterization of subsets of bone marrow-derived macrophages by flow cytometry analysis. J Leukoc Biol. 1985 Feb;37(2):121–136. doi: 10.1002/jlb.37.2.121. [DOI] [PubMed] [Google Scholar]
  43. Yamanashi Y., Fukushige S., Semba K., Sukegawa J., Miyajima N., Matsubara K., Yamamoto T., Toyoshima K. The yes-related cellular gene lyn encodes a possible tyrosine kinase similar to p56lck. Mol Cell Biol. 1987 Jan;7(1):237–243. doi: 10.1128/mcb.7.1.237. [DOI] [PMC free article] [PubMed] [Google Scholar]

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