Skip to main content
The EMBO Journal logoLink to The EMBO Journal
. 1986 Sep;5(9):2197–2202. doi: 10.1002/j.1460-2075.1986.tb04484.x

Evolutionary conserved close linkage of the c-fes/fps proto-oncogene and genetic sequences encoding a receptor-like protein.

A J Roebroek, J A Schalken, J A Leunissen, C Onnekink, H P Bloemers, W J Van de Ven
PMCID: PMC1167100  PMID: 3023061

Abstract

Recently we described that genetic sequences in the immediately upstream region of the c-fes/fps proto-oncogene, designated fur, constituted a transcription unit for a 4.5-kb mRNA. Here we present characteristics of the genetic organization of fur and some features of its putative translation product which we call furin. The nucleotide sequence of a 3.1-kbp fur-specific cDNA isolated from a human cDNA library revealed an open reading frame of 1,498 bp from which the 499 carboxy-terminal amino acids of the primary fur translational product could be deduced. Computer analysis indicated that furin contained a possible transmembrane domain which resembled that of class II MHC antigens. Furthermore, a cysteine-rich region was present. Significant homology, especially with respect to the topography of cysteine residues, was found between the cysteine-rich regions of the human insulin receptor, the human epidermal growth factor receptor and furin. From the data presented here we deduce that fur may encode a membrane-associated protein with a recognition function.

Full text

PDF
2197

Selected References

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

  1. Auffray C., Rougeon F. Purification of mouse immunoglobulin heavy-chain messenger RNAs from total myeloma tumor RNA. Eur J Biochem. 1980 Jun;107(2):303–314. doi: 10.1111/j.1432-1033.1980.tb06030.x. [DOI] [PubMed] [Google Scholar]
  2. Barbacid M., Beemon K., Devare S. G. Origin and functional properties of the major gene product of the Snyder-Theilen strain of feline sarcoma virus. Proc Natl Acad Sci U S A. 1980 Sep;77(9):5158–5162. doi: 10.1073/pnas.77.9.5158. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Church G. M., Gilbert W. Genomic sequencing. Proc Natl Acad Sci U S A. 1984 Apr;81(7):1991–1995. doi: 10.1073/pnas.81.7.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Claverie J. M., Sauvaget I. A new protein sequence data bank. Nature. 1985 Nov 7;318(6041):19–19. doi: 10.1038/318019a0. [DOI] [PubMed] [Google Scholar]
  5. Coussens L., Van Beveren C., Smith D., Chen E., Mitchell R. L., Isacke C. M., Verma I. M., Ullrich A. Structural alteration of viral homologue of receptor proto-oncogene fms at carboxyl terminus. Nature. 1986 Mar 20;320(6059):277–280. doi: 10.1038/320277a0. [DOI] [PubMed] [Google Scholar]
  6. Feldman R. A., Gabrilove J. L., Tam J. P., Moore M. A., Hanafusa H. Specific expression of the human cellular fps/fes-encoded protein NCP92 in normal and leukemic myeloid cells. Proc Natl Acad Sci U S A. 1985 Apr;82(8):2379–2383. doi: 10.1073/pnas.82.8.2379. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Fennewald S., van Santen V., Kieff E. Nucleotide sequence of an mRNA transcribed in latent growth-transforming virus infection indicates that it may encode a membrane protein. J Virol. 1984 Aug;51(2):411–419. doi: 10.1128/jvi.51.2.411-419.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Gray A., Dull T. J., Ullrich A. Nucleotide sequence of epidermal growth factor cDNA predicts a 128,000-molecular weight protein precursor. Nature. 1983 Jun 23;303(5919):722–725. doi: 10.1038/303722a0. [DOI] [PubMed] [Google Scholar]
  9. Green S., Walter P., Kumar V., Krust A., Bornert J. M., Argos P., Chambon P. Human oestrogen receptor cDNA: sequence, expression and homology to v-erb-A. Nature. 1986 Mar 13;320(6058):134–139. doi: 10.1038/320134a0. [DOI] [PubMed] [Google Scholar]
  10. Groffen J., Heisterkamp N., Grosveld F., Van de Ven W., Stephenson J. R. Isolation of human oncogene sequences (v-fes homolog) from a cosmid library. Science. 1982 Jun 4;216(4550):1136–1138. doi: 10.1126/science.6281890. [DOI] [PubMed] [Google Scholar]
  11. Gubler U., Hoffman B. J. A simple and very efficient method for generating cDNA libraries. Gene. 1983 Nov;25(2-3):263–269. doi: 10.1016/0378-1119(83)90230-5. [DOI] [PubMed] [Google Scholar]
  12. Hanahan D., Meselson M. Plasmid screening at high colony density. Gene. 1980 Jun;10(1):63–67. doi: 10.1016/0378-1119(80)90144-4. [DOI] [PubMed] [Google Scholar]
  13. Hollenberg S. M., Weinberger C., Ong E. S., Cerelli G., Oro A., Lebo R., Thompson E. B., Rosenfeld M. G., Evans R. M. Primary structure and expression of a functional human glucocorticoid receptor cDNA. Nature. 1985 Dec 19;318(6047):635–641. doi: 10.1038/318635a0. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Koeffler H. P., Golde D. W. Acute myelogenous leukemia: a human cell line responsive to colony-stimulating activity. Science. 1978 Jun 9;200(4346):1153–1154. doi: 10.1126/science.306682. [DOI] [PubMed] [Google Scholar]
  15. Kyte J., Doolittle R. F. A simple method for displaying the hydropathic character of a protein. J Mol Biol. 1982 May 5;157(1):105–132. doi: 10.1016/0022-2836(82)90515-0. [DOI] [PubMed] [Google Scholar]
  16. Lipman D. J., Pearson W. R. Rapid and sensitive protein similarity searches. Science. 1985 Mar 22;227(4693):1435–1441. doi: 10.1126/science.2983426. [DOI] [PubMed] [Google Scholar]
  17. MacDonald I., Levy J., Pawson T. Expression of the mammalian c-fes protein in hematopoietic cells and identification of a distinct fes-related protein. Mol Cell Biol. 1985 Oct;5(10):2543–2551. doi: 10.1128/mcb.5.10.2543. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Mathey-Prevot B., Hanafusa H., Kawai S. A cellular protein is immunologically crossreactive with and functionally homologous to the Fujinami sarcoma virus transforming protein. Cell. 1982 Apr;28(4):897–906. doi: 10.1016/0092-8674(82)90069-1. [DOI] [PubMed] [Google Scholar]
  19. Messing J., Vieira J. A new pair of M13 vectors for selecting either DNA strand of double-digest restriction fragments. Gene. 1982 Oct;19(3):269–276. doi: 10.1016/0378-1119(82)90016-6. [DOI] [PubMed] [Google Scholar]
  20. 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]
  21. Neckameyer W. S., Wang L. H. Nucleotide sequence of avian sarcoma virus UR2 and comparison of its transforming gene with other members of the tyrosine protein kinase oncogene family. J Virol. 1985 Mar;53(3):879–884. doi: 10.1128/jvi.53.3.879-884.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Ovchinnikov YuA Rhodopsin and bacteriorhodopsin: structure-function relationships. FEBS Lett. 1982 Nov 8;148(2):179–191. doi: 10.1016/0014-5793(82)80805-3. [DOI] [PubMed] [Google Scholar]
  23. Pfaff S. L., Zhou R. P., Young J. C., Hayflick J., Duesberg P. H. Defining the borders of the chicken proto-fps gene, a precursor of Fujinami sarcoma virus. Virology. 1985 Oct 30;146(2):307–314. doi: 10.1016/0042-6822(85)90014-5. [DOI] [PubMed] [Google Scholar]
  24. Pfeffer S., Ullrich A. Epidermal growth factor. Is the precursor a receptor? Nature. 1985 Jan 17;313(5999):184–184. doi: 10.1038/313184a0. [DOI] [PubMed] [Google Scholar]
  25. Roebroek A. J., Schalken J. A., Bussemakers M. J., van Heerikhuizen H., Onnekink C., Debruyne F. M., Bloemers H. P., Van de Ven W. J. Characterization of human c-fes/fps reveals a new transcription unit (fur) in the immediately upstream region of the proto-oncogene. Mol Biol Rep. 1986;11(2):117–125. doi: 10.1007/BF00364823. [DOI] [PubMed] [Google Scholar]
  26. Roebroek A. J., Schalken J. A., Verbeek J. S., Van den Ouweland A. M., Onnekink C., Bloemers H. P., Van de Ven W. J. The structure of the human c-fes/fps proto-oncogene. EMBO J. 1985 Nov;4(11):2897–2903. doi: 10.1002/j.1460-2075.1985.tb04020.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Sanger F., Nicklen S., Coulson A. R. DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463–5467. doi: 10.1073/pnas.74.12.5463. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Schenning L., Larhammar D., Bill P., Wiman K., Jonsson A. K., Rask L., Peterson P. A. Both alpha and beta chains of HLA-DC class II histocompatibility antigens display extensive polymorphism in their amino-terminal domains. EMBO J. 1984 Feb;3(2):447–452. doi: 10.1002/j.1460-2075.1984.tb01826.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. 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]
  30. Slamon D. J., deKernion J. B., Verma I. M., Cline M. J. Expression of cellular oncogenes in human malignancies. Science. 1984 Apr 20;224(4646):256–262. doi: 10.1126/science.6538699. [DOI] [PubMed] [Google Scholar]
  31. Staden R. An interactive graphics program for comparing and aligning nucleic acid and amino acid sequences. Nucleic Acids Res. 1982 May 11;10(9):2951–2961. doi: 10.1093/nar/10.9.2951. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Südhof T. C., Goldstein J. L., Brown M. S., Russell D. W. The LDL receptor gene: a mosaic of exons shared with different proteins. Science. 1985 May 17;228(4701):815–822. doi: 10.1126/science.2988123. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Ullrich A., Bell J. R., Chen E. Y., Herrera R., Petruzzelli L. M., Dull T. J., Gray A., Coussens L., Liao Y. C., Tsubokawa M. Human insulin receptor and its relationship to the tyrosine kinase family of oncogenes. 1985 Feb 28-Mar 6Nature. 313(6005):756–761. doi: 10.1038/313756a0. [DOI] [PubMed] [Google Scholar]
  34. Ullrich A., Coussens L., Hayflick J. S., Dull T. J., Gray A., Tam A. W., Lee J., Yarden Y., Libermann T. A., Schlessinger J. Human epidermal growth factor receptor cDNA sequence and aberrant expression of the amplified gene in A431 epidermoid carcinoma cells. 1984 May 31-Jun 6Nature. 309(5967):418–425. doi: 10.1038/309418a0. [DOI] [PubMed] [Google Scholar]
  35. Verbeek J. S., van den Ouweland A. M., Schalken J. A., Roebroek A. J., Onnekink C., Bloemers H. P., van de Ven W. J. Molecular cloning of the feline c-fes proto-oncogene and construction of a chimeric transforming gene. Gene. 1985;35(1-2):33–43. doi: 10.1016/0378-1119(85)90155-6. [DOI] [PubMed] [Google Scholar]
  36. Weinberger C., Hollenberg S. M., Rosenfeld M. G., Evans R. M. Domain structure of human glucocorticoid receptor and its relationship to the v-erb-A oncogene product. Nature. 1985 Dec 19;318(6047):670–672. doi: 10.1038/318670a0. [DOI] [PubMed] [Google Scholar]
  37. Yamamoto K. R. Steroid receptor regulated transcription of specific genes and gene networks. Annu Rev Genet. 1985;19:209–252. doi: 10.1146/annurev.ge.19.120185.001233. [DOI] [PubMed] [Google Scholar]
  38. Yamamoto T., Davis C. G., Brown M. S., Schneider W. J., Casey M. L., Goldstein J. L., Russell D. W. The human LDL receptor: a cysteine-rich protein with multiple Alu sequences in its mRNA. Cell. 1984 Nov;39(1):27–38. doi: 10.1016/0092-8674(84)90188-0. [DOI] [PubMed] [Google Scholar]
  39. Young D., Waitches G., Birchmeier C., Fasano O., Wigler M. Isolation and characterization of a new cellular oncogene encoding a protein with multiple potential transmembrane domains. Cell. 1986 Jun 6;45(5):711–719. doi: 10.1016/0092-8674(86)90785-3. [DOI] [PubMed] [Google Scholar]
  40. van den Ouweland A. M., Breuer M. L., Steenbergh P. H., Schalken J. A., Bloemers H. P., Van de Ven W. J. Comparative analysis of the human and feline c-sis proto-oncogenes. Identification of 5' human c-sis coding sequences that are not homologous to the transforming gene of simian sarcoma virus. Biochim Biophys Acta. 1985 Jun 24;825(2):140–147. doi: 10.1016/0167-4781(85)90097-1. [DOI] [PubMed] [Google Scholar]

Articles from The EMBO Journal are provided here courtesy of Nature Publishing Group

RESOURCES