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Cloning of decay-accelerating factor suggests novel use of splicing to generate two proteins

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Abstract

Decay-accelerating factor (DAF), a glycoprotein that is anchored to the cell membrane by phosphatidylinositol1,2, binds activated complement fragments C3b and C4b, thereby inhibiting amplification of the complement cascade on host cell membranes3–5. Here, we report the molecular cloning of human DAF from HeLa cells. Analysis of DAF complementary DNAs revealed two classes of DAF messenger RNA, one apparently derived from the other by a splicing event that causes a coding frameshift near the C terminus. The apparent 'intron' sequence contains an Alu family member and encodes contiguous protein sequence. Two DAF proteins are therefore possible, having divergent C-terminal domains which differ in their hydrophobicity. Both mRNAs are found on polysomes, suggesting that both are translated. We propose that the major (90%) spliced DAF mRNA encodes membrane-bound DAF whereas the minor (10%) unspliced DAF mRNA may encode secreted DAF and we present expression data supporting this. The deduced DAF sequence contains four repeating units homologous to a consensus repeat found in a recently described family of complement proteins6.

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References

  1. Davitz, M. A., Low, M. G. & Nussenzweig, V. J. exp. Med. 163, 1150–1161 (1986).

    Article  CAS  Google Scholar 

  2. Medof, M. E., Haas, R., Walter, E. I. & Rosenberry, T. L. Fed. Proc. 45, 382 (1986).

    Google Scholar 

  3. Nicholson-Weller, A. J. et al. J. Immun. 129, 184–189 (1982).

    CAS  PubMed  Google Scholar 

  4. Medof, M. E., Kinoshita, T. & Nussenzweig, V. J. exp. Med. 160, 1558–1578 (1984).

    Article  CAS  Google Scholar 

  5. Kinoshita, T., Medof, M. E. & Nussenzweig, V. J. Immun. 136, 3390–3395 (1986).

    CAS  PubMed  Google Scholar 

  6. Reid, K. B. M. et al. Immun. Today 7, 230 (1986).

    Article  CAS  Google Scholar 

  7. Anderson, S. & Kingston, I. B. Proc. natn. Acad. Sci. U.S.A. 80, 6836–6842 (1983).

    ADS  Google Scholar 

  8. Ullrich, A. et al. Nature 316, 418–425 (1984).

    Article  ADS  Google Scholar 

  9. Davitz, M. A., Schiesinger, D. & Nussenzweig, V. J. Immun. Meth. (in the press).

  10. Kozak, M. Microbiol. Rev. 57, 1–45 (1983).

    Google Scholar 

  11. Cummings, R. D. et al. J. biol. Chem. 258, 15261–15273 (1983).

    CAS  PubMed  Google Scholar 

  12. Russell, D. W. et al. Cell 37, 577–585 (1984).

    Article  CAS  Google Scholar 

  13. Mount, S. M. Nucleic Acids Res. 10, 459–472 (1982).

    Article  CAS  Google Scholar 

  14. Sharp, P. A. Cell 23, 643–646 (1981).

    Article  CAS  Google Scholar 

  15. Schmidt, C. W. & Jelinek, W. R. Science 216, 1065–1070 (1982).

    Article  ADS  Google Scholar 

  16. Proudfoot, N. J. & Brownlee, G. G. Nature 263, 211–214 (1976).

    Article  ADS  CAS  Google Scholar 

  17. Medof, M. E. et al. Complement 2, 53 (1985).

    Google Scholar 

  18. Low, M. G., Ferguson, M. A. J., Futerman, A. H. & Silman, I. Trends biochem. Sci. 11, 212–215 (1986).

    Article  CAS  Google Scholar 

  19. Low, M. G. & Kincade, P. W. Nature 318, 62–64 (1985).

    Article  ADS  CAS  Google Scholar 

  20. Tse, A. G. D. et al. Science 230, 1003–1008 (1985).

    Article  ADS  CAS  Google Scholar 

  21. Ferguson, M. A. J. et al. J. biol. Chem. 261, 356–362 (1986).

    CAS  PubMed  Google Scholar 

  22. Early, P. et al. Cell 20, 313–319 (1980).

    Article  CAS  Google Scholar 

  23. Towbin, H., Stachlin, T. & Gorden, J. Proc. natn. Acad. Sci. U.S.A. 76, 4350 (1979).

    Article  ADS  CAS  Google Scholar 

  24. Messing, J., Crea, R. & Seeburg, P. H. Nucleic Acids Res. 9, 309–321 (1981).

    Article  CAS  Google Scholar 

  25. Sanger, F., Nicklew, S. & Coulson, A. R. Proc. natn. Acad. Sci. U.S.A. 74, 5463–5467 (1977).

    Article  ADS  CAS  Google Scholar 

  26. Vergara, U. et al. Molec. biochem. Parasitol. 14, 283–292 (1985).

    Article  CAS  Google Scholar 

  27. Green, N. et al. Cell 28, 477–487 (1982).

    Article  CAS  Google Scholar 

  28. Kyte, J. & Doolittle, R. F. J. molec. Biol. 157, 105 (1982).

    Article  CAS  Google Scholar 

  29. Maniatis, T., Fritsch, E. F. & Sambrook, J. Molecular Cloning; a Laboratory Manual, 202–203 (Cold Spring Harbor Laboratory, New York, 1982).

    Google Scholar 

  30. Goddard, J. M., Caput, D., Williams, S. R. and Martin, D. W., Jr Proc. natn. Acad. Sci. U.S.A. 80, 4281–4285 (1983).

    Article  ADS  CAS  Google Scholar 

  31. Maniatis, T., Fritsch, E. F. & Sambrook, J. Molecular Cloning; a Laboratory Manual, 122–124 (Cold Spring Harbor Laboratory, New York, 1982).

    Google Scholar 

  32. Taylor, J. M., Illmensee, R. & Summers, S. Biochim. biophys. Acta 442, 324–330 (1976).

    Article  CAS  Google Scholar 

  33. Wood, W. I. et al. Proc. natn. Acad. Sci. U.S.A. 82, 1585–1588 (1985).

    Article  ADS  CAS  Google Scholar 

  34. Gorman, C. M. et al. Proc. natn. Acad. Sci. U.S.A. 79, 6777–6781 (1982).

    Article  ADS  CAS  Google Scholar 

  35. Simonsen, C. C. & Levinson, A. D. Proc. natn. Acad. Sci. U.S.A. 80, 2495–2499 (1983).

    Article  ADS  CAS  Google Scholar 

  36. Wigler, M. et al. Proc. natn. Acad. Sci. U.S.A. 76, 1373–1376 (1979).

    Article  ADS  CAS  Google Scholar 

  37. Gottlieb et al. J. Cell Biol. 102, 1242–1255 (1986).

    Article  CAS  Google Scholar 

  38. Rose, J. K. & Bergmann, J. E. Cell 30, 753–762 (1982).

    Article  CAS  Google Scholar 

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Author notes

  1. Michael A. Davitz and Victor Nussenzweig: Department of Pathology, New York University School of Medicine, New York, New York 10016, USA

  2. Michael A. Davitz: Department of Environmental Medicine, New York University School of Medicine, New York, New York 10016, USA

Authors and Affiliations

  1. Genentech, Inc., 460 Point San Bruno Boulevard, South San Francisco, California, 94080, USA

    Ingrid W. Caras, Michael A. Davitz, Lucy Rhee, Greg Weddell, David W. Martin Jr & Victor Nussenzweig

Authors
  1. Ingrid W. Caras
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  2. Michael A. Davitz
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  3. Lucy Rhee
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  4. Greg Weddell
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  5. David W. Martin Jr
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  6. Victor Nussenzweig
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Caras, I., Davitz, M., Rhee, L. et al. Cloning of decay-accelerating factor suggests novel use of splicing to generate two proteins. Nature 325, 545–549 (1987). https://doi.org/10.1038/325545a0

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  • DOI: https://doi.org/10.1038/325545a0

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