Skip to main content
NCBI home page
The Journal of Cell Biology logoLink to The Journal of Cell Biology
. 1989 Dec 1;109(6):3129–3136. doi: 10.1083/jcb.109.6.3129

Expression of the fgr protooncogene product as a function of myelomonocytic cell maturation

PMCID: PMC2115966  PMID: 2687293

Abstract

The fgr protooncogene is a member of the src family of protein tyrosine kinases. Recent studies have shown that normal myelomonocytic cells and tissue macrophages are the major sites of fgr mRNA expression. In the present study, we have identified the fgr protooncogene protein product in HL60 cells and have examined its expression as a function of HL60 cell maturation. Whether induced toward monocytic or granulocytic lineages, p55c-fgr accumulated in HL60 cells during maturation. In differentiated cells, the protein was active as a protein tyrosine kinase and was localized to peripheral cell membranes. Demonstration that a myristyl group was covalently bound to the protein probably accounted for its subcellular distribution. These findings establish developmental regulation of p55c-fgr in a lineage that represents its natural site of expression.

Full Text

The Full Text of this article is available as a PDF (1.7 MB).

Selected References

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

  1. Barnekow A., Gessler M. Activation of the pp60c-src kinase during differentiation of monomyelocytic cells in vitro. EMBO J. 1986 Apr;5(4):701–705. doi: 10.1002/j.1460-2075.1986.tb04270.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Breitman T. R., Selonick S. E., Collins S. J. Induction of differentiation of the human promyelocytic leukemia cell line (HL-60) by retinoic acid. Proc Natl Acad Sci U S A. 1980 May;77(5):2936–2940. doi: 10.1073/pnas.77.5.2936. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Buss J. E., Sefton B. M. Myristic acid, a rare fatty acid, is the lipid attached to the transforming protein of Rous sarcoma virus and its cellular homolog. J Virol. 1985 Jan;53(1):7–12. doi: 10.1128/jvi.53.1.7-12.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. 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]
  5. Collins S. J., Gallo R. C., Gallagher R. E. Continuous growth and differentiation of human myeloid leukaemic cells in suspension culture. Nature. 1977 Nov 24;270(5635):347–349. doi: 10.1038/270347a0. [DOI] [PubMed] [Google Scholar]
  6. Collins S. J., Ruscetti F. W., Gallagher R. E., Gallo R. C. Terminal differentiation of human promyelocytic leukemia cells induced by dimethyl sulfoxide and other polar compounds. Proc Natl Acad Sci U S A. 1978 May;75(5):2458–2462. doi: 10.1073/pnas.75.5.2458. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Cooper J. A., Esch F. S., Taylor S. S., Hunter T. Phosphorylation sites in enolase and lactate dehydrogenase utilized by tyrosine protein kinases in vivo and in vitro. J Biol Chem. 1984 Jun 25;259(12):7835–7841. [PubMed] [Google Scholar]
  8. Cross F. R., Garber E. A., Pellman D., Hanafusa H. A short sequence in the p60src N terminus is required for p60src myristylation and membrane association and for cell transformation. Mol Cell Biol. 1984 Sep;4(9):1834–1842. doi: 10.1128/mcb.4.9.1834. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Doolittle R. F., Hunkapiller M. W., Hood L. E., Devare S. G., Robbins K. C., Aaronson S. A., Antoniades H. N. Simian sarcoma virus onc gene, v-sis, is derived from the gene (or genes) encoding a platelet-derived growth factor. Science. 1983 Jul 15;221(4607):275–277. doi: 10.1126/science.6304883. [DOI] [PubMed] [Google Scholar]
  10. Downward J., Yarden Y., Mayes E., Scrace G., Totty N., Stockwell P., Ullrich A., Schlessinger J., Waterfield M. D. Close similarity of epidermal growth factor receptor and v-erb-B oncogene protein sequences. Nature. 1984 Feb 9;307(5951):521–527. doi: 10.1038/307521a0. [DOI] [PubMed] [Google Scholar]
  11. Furth M. E., Davis L. J., Fleurdelys B., Scolnick E. M. Monoclonal antibodies to the p21 products of the transforming gene of Harvey murine sarcoma virus and of the cellular ras gene family. J Virol. 1982 Jul;43(1):294–304. doi: 10.1128/jvi.43.1.294-304.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. 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]
  13. 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]
  14. Inoue K., Ikawa S., Semba K., Sukegawa J., Yamamoto T., Toyoshima K. Isolation and sequencing of cDNA clones homologous to the v-fgr oncogene from a human B lymphocyte cell line, IM-9. Oncogene. 1987;1(3):301–304. [PubMed] [Google Scholar]
  15. Jove R., Hanafusa H. Cell transformation by the viral src oncogene. Annu Rev Cell Biol. 1987;3:31–56. doi: 10.1146/annurev.cb.03.110187.000335. [DOI] [PubMed] [Google Scholar]
  16. Katamine S., Notario V., Rao C. D., Miki T., Cheah M. S., Tronick S. R., Robbins K. C. Primary structure of the human fgr proto-oncogene product p55c-fgr. Mol Cell Biol. 1988 Jan;8(1):259–266. doi: 10.1128/mcb.8.1.259. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Kawakami T., Kawakami Y., Aaronson S. A., Robbins K. C. Acquisition of transforming properties by FYN, a normal SRC-related human gene. Proc Natl Acad Sci U S A. 1988 Jun;85(11):3870–3874. doi: 10.1073/pnas.85.11.3870. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Ley T. J., Connolly N. L., Katamine S., Cheah M. S., Senior R. M., Robbins K. C. Tissue-specific expression and developmental regulation of the human fgr proto-oncogene. Mol Cell Biol. 1989 Jan;9(1):92–99. doi: 10.1128/mcb.9.1.92. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Lipsich L. A., Lewis A. J., Brugge J. S. Isolation of monoclonal antibodies that recognize the transforming proteins of avian sarcoma viruses. J Virol. 1983 Nov;48(2):352–360. doi: 10.1128/jvi.48.2.352-360.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Lutton J. K., Frederich R. C., Jr, Perkins J. P. Isolation of adenylate cyclase-enriched membranes from mammalian cells using concanavalin A. J Biol Chem. 1979 Nov 25;254(22):11181–11184. [PubMed] [Google Scholar]
  21. 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]
  22. Pellman D., Garber E. A., Cross F. R., Hanafusa H. Fine structural mapping of a critical NH2-terminal region of p60src. Proc Natl Acad Sci U S A. 1985 Mar;82(6):1623–1627. doi: 10.1073/pnas.82.6.1623. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Rovera G., Santoli D., Damsky C. Human promyelocytic leukemia cells in culture differentiate into macrophage-like cells when treated with a phorbol diester. Proc Natl Acad Sci U S A. 1979 Jun;76(6):2779–2783. doi: 10.1073/pnas.76.6.2779. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Sariban E., Mitchell T., Kufe D. Expression of the c-fms proto-oncogene during human monocytic differentiation. Nature. 1985 Jul 4;316(6023):64–66. doi: 10.1038/316064a0. [DOI] [PubMed] [Google Scholar]
  25. Sefton B. M., Trowbridge I. S., Cooper J. A., Scolnick E. M. The transforming proteins of Rous sarcoma virus, Harvey sarcoma virus and Abelson virus contain tightly bound lipid. Cell. 1982 Dec;31(2 Pt 1):465–474. doi: 10.1016/0092-8674(82)90139-8. [DOI] [PubMed] [Google Scholar]
  26. Shalloway D., Johnson P. J., Freed E. O., Coulter D., Flood W. A., Jr Transformation of NIH 3T3 cells by cotransfection with c-src and nuclear oncogenes. Mol Cell Biol. 1987 Oct;7(10):3582–3590. doi: 10.1128/mcb.7.10.3582. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. 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]
  28. Srivastava S. K., Yuasa Y., Reynolds S. H., Aaronson S. A. Effects of two major activating lesions on the structure and conformation of human ras oncogene products. Proc Natl Acad Sci U S A. 1985 Jan;82(1):38–42. doi: 10.1073/pnas.82.1.38. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Sukegawa J., Semba K., Yamanashi Y., Nishizawa M., Miyajima N., Yamamoto T., Toyoshima K. Characterization of cDNA clones for the human c-yes gene. Mol Cell Biol. 1987 Jan;7(1):41–47. doi: 10.1128/mcb.7.1.41. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Takeya T., Hanafusa H. Structure and sequence of the cellular gene homologous to the RSV src gene and the mechanism for generating the transforming virus. Cell. 1983 Mar;32(3):881–890. doi: 10.1016/0092-8674(83)90073-9. [DOI] [PubMed] [Google Scholar]
  31. 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]
  32. Waterfield M. D., Scrace G. T., Whittle N., Stroobant P., Johnsson A., Wasteson A., Westermark B., Heldin C. H., Huang J. S., Deuel T. F. Platelet-derived growth factor is structurally related to the putative transforming protein p28sis of simian sarcoma virus. Nature. 1983 Jul 7;304(5921):35–39. doi: 10.1038/304035a0. [DOI] [PubMed] [Google Scholar]
  33. Willman C. L., Stewart C. C., Griffith J. K., Stewart S. J., Tomasi T. B. Differential expression and regulation of the c-src and c-fgr protooncogenes in myelomonocytic cells. Proc Natl Acad Sci U S A. 1987 Jul;84(13):4480–4484. doi: 10.1073/pnas.84.13.4480. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Ziegler S. F., Wilson C. B., Perlmutter R. M. Augmented expression of a myeloid-specific protein tyrosine kinase gene (hck) after macrophage activation. J Exp Med. 1988 Nov 1;168(5):1801–1810. doi: 10.1084/jem.168.5.1801. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from The Journal of Cell Biology are provided here courtesy of The Rockefeller University Press

RESOURCES