Skip to main content
PMC home page
Molecular and Cellular Biology logoLink to Molecular and Cellular Biology
. 1986 Feb;6(2):511–517. doi: 10.1128/mcb.6.2.511

Structure, expression, and chromosomal location of the human c-fgr gene.

M Nishizawa, K Semba, M C Yoshida, T Yamamoto, M Sasaki, K Toyoshima
PMCID: PMC367540  PMID: 3023853

Abstract

The nucleotide sequence of seven exons of the human c-fgr gene, a cellular homolog of the oncogene of Gardner-Rasheed feline sarcoma virus, was determined. Twenty-six independent genomic clones were obtained from a human gene library with a DNA clone of Y73 avian sarcoma virus oncogene, v-yes, as a probe under relaxed hybridization conditions. Restriction mapping and partial sequence analyses revealed that two of these clones were derived from the c-fgr gene, distinct from the c-yes gene. Interestingly, the splicing points of the c-fgr gene were identical with those of the c-src gene throughout the seven exons, suggesting that the two proto-oncogenes were generated by gene duplication of an ancestral gene containing intervening sequences. On RNA blot hybridization the major transcript was found to be 2.6 kilobase long. Two additional transcripts of 3.5 and 4.7 kilobases were also detected. Furthermore, karyotype analysis of several human-mouse hybrid cells and Southern blot analyses of DNAs of the hybrids with a human c-fgr locus-specific probe showed that this gene is located on chromosome 1.

Full text

PDF
511

Images in this article

515Image
on p.515
515Image
on p.515

Selected References

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

  1. Anderson S. K., Gibbs C. P., Tanaka A., Kung H. J., Fujita D. J. Human cellular src gene: nucleotide sequence and derived amino acid sequence of the region coding for the carboxy-terminal two-thirds of pp60c-src. Mol Cell Biol. 1985 May;5(5):1122–1129. doi: 10.1128/mcb.5.5.1122. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bishop J. M. Cellular oncogenes and retroviruses. Annu Rev Biochem. 1983;52:301–354. doi: 10.1146/annurev.bi.52.070183.001505. [DOI] [PubMed] [Google Scholar]
  3. Bonner T. I., Kerby S. B., Sutrave P., Gunnell M. A., Mark G., Rapp U. R. Structure and biological activity of human homologs of the raf/mil oncogene. Mol Cell Biol. 1985 Jun;5(6):1400–1407. doi: 10.1128/mcb.5.6.1400. [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. Davis M., Malcolm S., Hall A., Marshall C. J. Localisation of the human N-ras oncogene to chromosome 1cen - p21 by in situ hybridisation. EMBO J. 1983;2(12):2281–2283. doi: 10.1002/j.1460-2075.1983.tb01735.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Denhardt D. T. A membrane-filter technique for the detection of complementary DNA. Biochem Biophys Res Commun. 1966 Jun 13;23(5):641–646. doi: 10.1016/0006-291x(66)90447-5. [DOI] [PubMed] [Google Scholar]
  7. Efstratiadis A., Posakony J. W., Maniatis T., Lawn R. M., O'Connell C., Spritz R. A., DeRiel J. K., Forget B. G., Weissman S. M., Slightom J. L. The structure and evolution of the human beta-globin gene family. Cell. 1980 Oct;21(3):653–668. doi: 10.1016/0092-8674(80)90429-8. [DOI] [PubMed] [Google Scholar]
  8. Fahey J. L., Buell D. N., Sox H. C. Proliferation and differentiation of lymphoid cells: studies with human lymphoid cell lines and immunoglobulin synthesis. Ann N Y Acad Sci. 1971 Dec 31;190:221–234. doi: 10.1111/j.1749-6632.1971.tb13537.x. [DOI] [PubMed] [Google Scholar]
  9. Fukuhara S., Rowley J. D., Variakojis D., Golomb H. M. Chromosome abnormalities in poorly differentiated lymphocytic lymphoma. Cancer Res. 1979 Aug;39(8):3119–3128. [PubMed] [Google Scholar]
  10. 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]
  11. Groffen J., Heisterkamp N., Shibuya M., Hanafusa H., Stephenson J. R. Transforming genes of avian (v-fps) and mammalian (v-fes) retroviruses correspond to a common cellular locus. Virology. 1983 Mar;125(2):480–486. doi: 10.1016/0042-6822(83)90219-2. [DOI] [PubMed] [Google Scholar]
  12. Hall A., Marshall C. J., Spurr N. K., Weiss R. A. Identification of transforming gene in two human sarcoma cell lines as a new member of the ras gene family located on chromosome 1. Nature. 1983 Jun 2;303(5916):396–400. doi: 10.1038/303396a0. [DOI] [PubMed] [Google Scholar]
  13. Hoffman-Falk H., Einat P., Shilo B. Z., Hoffmann F. M. Drosophila melanogaster DNA clones homologous to vertebrate oncogenes: evidence for a common ancestor to the src and abl cellular genes. Cell. 1983 Feb;32(2):589–598. doi: 10.1016/0092-8674(83)90478-6. [DOI] [PubMed] [Google Scholar]
  14. Hoffmann F. M., Fresco L. D., Hoffman-Falk H., Shilo B. Z. Nucleotide sequences of the Drosophila src and abl homologs: conservation and variability in the src family oncogenes. Cell. 1983 Dec;35(2 Pt 1):393–401. doi: 10.1016/0092-8674(83)90172-1. [DOI] [PubMed] [Google Scholar]
  15. Itohara S., Hirata K., Inoue M., Hatsuoka M., Sato A. Isolation of a sarcoma virus from a spontaneous chicken tumor. Gan. 1978 Dec;69(6):825–830. [PubMed] [Google Scholar]
  16. Jansen H. W., Lurz R., Bister K., Bonner T. I., Mark G. E., Rapp U. R. Homologous cell-derived oncogenes in avian carcinoma virus MH2 and murine sarcoma virus 3611. Nature. 1984 Jan 19;307(5948):281–284. doi: 10.1038/307281a0. [DOI] [PubMed] [Google Scholar]
  17. Kawai S., Yoshida M., Segawa K., Sugiyama H., Ishizaki R., Toyoshima K. Characterization of Y73, an avian sarcoma virus: a unique transforming gene and its product, a phosphopolyprotein with protein kinase activity. Proc Natl Acad Sci U S A. 1980 Oct;77(10):6199–6203. doi: 10.1073/pnas.77.10.6199. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. 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]
  19. Le Beau M. M., Westbrook C. A., Diaz M. O., Rowley J. D. Evidence for two distinct c-src loci on human chromosomes 1 and 20. Nature. 1984 Nov 1;312(5989):70–71. doi: 10.1038/312070a0. [DOI] [PubMed] [Google Scholar]
  20. Lehrach H., Diamond D., Wozney J. M., Boedtker H. RNA molecular weight determinations by gel electrophoresis under denaturing conditions, a critical reexamination. Biochemistry. 1977 Oct 18;16(21):4743–4751. doi: 10.1021/bi00640a033. [DOI] [PubMed] [Google Scholar]
  21. Maniatis T., Fritsch E. F., Lauer J., Lawn R. M. The molecular genetics of human hemoglobins. Annu Rev Genet. 1980;14:145–178. doi: 10.1146/annurev.ge.14.120180.001045. [DOI] [PubMed] [Google Scholar]
  22. Maniatis T., Hardison R. C., Lacy E., Lauer J., O'Connell C., Quon D., Sim G. K., Efstratiadis A. The isolation of structural genes from libraries of eucaryotic DNA. Cell. 1978 Oct;15(2):687–701. doi: 10.1016/0092-8674(78)90036-3. [DOI] [PubMed] [Google Scholar]
  23. Messing J. New M13 vectors for cloning. Methods Enzymol. 1983;101:20–78. doi: 10.1016/0076-6879(83)01005-8. [DOI] [PubMed] [Google Scholar]
  24. Mount S. M. A catalogue of splice junction sequences. Nucleic Acids Res. 1982 Jan 22;10(2):459–472. doi: 10.1093/nar/10.2.459. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Naharro G., Dunn C. Y., Robbins K. C. Analysis of the primary translational product and integrated DNA of a new feline sarcoma virus, GR-FeSV. Virology. 1983 Mar;125(2):502–507. doi: 10.1016/0042-6822(83)90223-4. [DOI] [PubMed] [Google Scholar]
  26. Naharro G., Robbins K. C., Reddy E. P. Gene product of v-fgr onc: hybrid protein containing a portion of actin and a tyrosine-specific protein kinase. Science. 1984 Jan 6;223(4631):63–66. doi: 10.1126/science.6318314. [DOI] [PubMed] [Google Scholar]
  27. Naharro G., Tronick S. R., Rasheed S., Gardner M. B., Aaronson S. A., Robbins K. C. Molecular cloning of integrated Gardner-Rasheed feline sarcoma virus: genetic structure of its cell-derived sequence differs from that of other tyrosine kinase-coding onc genes. J Virol. 1983 Sep;47(3):611–619. doi: 10.1128/jvi.47.3.611-619.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Nishizawa M., Semba K., Yamamoto T., Toyoshima K. Human c-f gr gene does not contain coding sequence for actin-like protein. Jpn J Cancer Res. 1985 Mar;76(3):155–159. [PubMed] [Google Scholar]
  29. Norrander J., Kempe T., Messing J. Construction of improved M13 vectors using oligodeoxynucleotide-directed mutagenesis. Gene. 1983 Dec;26(1):101–106. doi: 10.1016/0378-1119(83)90040-9. [DOI] [PubMed] [Google Scholar]
  30. 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]
  31. Rasheed S., Barbacid M., Aaronson S., Gardner M. B. Origin and biological properties of a new feline sarcoma virus. Virology. 1982 Feb;117(1):238–244. doi: 10.1016/0042-6822(82)90522-0. [DOI] [PubMed] [Google Scholar]
  32. Ryan J., Barker P. E., Shimizu K., Wigler M., Ruddle F. H. Chromosomal assignment of a family of human oncogenes. Proc Natl Acad Sci U S A. 1983 Jul;80(14):4460–4463. doi: 10.1073/pnas.80.14.4460. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Semba K., Yamanashi Y., Nishizawa M., Sukegawa J., Yoshida M., Sasaki M., Yamamoto T., Toyoshima K. Location of the c-yes gene on the human chromosome and its expression in various tissues. Science. 1985 Mar 1;227(4690):1038–1040. doi: 10.1126/science.2983418. [DOI] [PubMed] [Google Scholar]
  34. Shimizu K., Goldfarb M., Perucho M., Wigler M. Isolation and preliminary characterization of the transforming gene of a human neuroblastoma cell line. Proc Natl Acad Sci U S A. 1983 Jan;80(2):383–387. doi: 10.1073/pnas.80.2.383. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Simon M. A., Kornberg T. B., Bishop J. M. Three loci related to the src oncogene and tyrosine-specific protein kinase activity in Drosophila. Nature. 1983 Apr 28;302(5911):837–839. doi: 10.1038/302837a0. [DOI] [PubMed] [Google Scholar]
  36. Takeya T., Feldman R. A., Hanafusa H. DNA sequence of the viral and cellular src gene of chickens. 1. Complete nucleotide sequence of an EcoRI fragment of recovered avian sarcoma virus which codes for gp37 and pp60src. J Virol. 1982 Oct;44(1):1–11. doi: 10.1128/jvi.44.1.1-11.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. 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]
  38. Wang J. Y., Ledley F., Goff S., Lee R., Groner Y., Baltimore D. The mouse c-abl locus: molecular cloning and characterization. Cell. 1984 Feb;36(2):349–356. doi: 10.1016/0092-8674(84)90228-9. [DOI] [PubMed] [Google Scholar]
  39. Yoshida M. C., Sasaki M., Mise K., Semba K., Nishizawa M., Yamamoto T., Toyoshima K. Regional mapping of the human proto-oncogene c-yes-1 to chromosome 18 at band q21.3. Jpn J Cancer Res. 1985 Jul;76(7):559–562. [PubMed] [Google Scholar]

Articles from Molecular and Cellular Biology are provided here courtesy of Taylor & Francis

RESOURCES