Identification of a specific lns(l,3,4,5)P4-binding protein as a member of the GAP1 family (original) (raw)

Nature volume 376, pages 527–530 (1995)Cite this article

Abstract

INOSITOL 1,3,4,5-tetrakisphosphate (Ins(l,3,4,5)P4) is produced rapidly from inositol 1,4,5-trisphosphate (Ins(l,4,5)P3) in stimulated cells1,2. Despite extensive experimentation, no clearly defined cellular function has yet been described for this inositol phosphate. Binding sites specific for Ins(l,3,4,5)P4 have been identified in several tissues3,4, and we have purified one such protein to homogeneity5. Its high affinity for Ins(l,3,4,5)P4, and its exquisite specificity for this isomeric configuration5,6, suggest it may be an Ins(l,3,4,5)P4 receptor. Here we report the cloning and characterization of this protein as a GTPase-activating protein, specifically a member of the GAP1 family. In vitro it shows GAP activity against both Rap and Ras, but only the Ras GAP activity is inhibited by phospholipids and is specifically stimulated by Ins(l,3,4,5)P4.

This is a preview of subscription content, access via your institution

Access options

Subscribe to this journal

Receive 51 print issues and online access

$199.00 per year

only $3.90 per issue

Buy this article

Prices may be subject to local taxes which are calculated during checkout

Additional access options:

Similar content being viewed by others

References

  1. Irvine, R. F. in Inositol Phosphates and Calcium Signalling (ed. Putney, J. W. Jr.) 161–185 (Raven Press, New York, 1992).
    Google Scholar
  2. Batty, I. R., Nahorski, S. R. & Irvine, R. F. Biochem. J. 232, 211–215 (1985).
    Article CAS Google Scholar
  3. Cullen, P. J. & Irvine, R. F. Biochem. J. 288, 149–154 (1992).
    Article CAS Google Scholar
  4. Irvine, R. F. & Cullen, P. J. Curr. Biol. 3, 540–543 (1993).
    Article CAS Google Scholar
  5. Cullen, P. J. Dawson, A. P. & Irvine, R. F. Biochem. J. 305, 139–143 (1995).
    Article CAS Google Scholar
  6. Cullen, P. J. Chung, S.-K., Chang Y-T., Dawson, A. P. & Irvine, R. F. FEBS Lett. 358, 240–243 (1995).
    Article CAS Google Scholar
  7. Gaul, U., Mardon, G. & Rubin, G. M. Cell 68, 1007–1019 (1992).
    Article CAS Google Scholar
  8. Maekawa, M. et al. Molec. cell. Biol. 14, 6879–6885 (1994).
    Article CAS Google Scholar
  9. Gibson, T. J., Hyvonen, M., Musacchio, A., Saraste, M. & Birney, E. Trends biol. Sci. 19, 349–353 (1994).
    Article CAS Google Scholar
  10. Pawson, T. Nature 373, 573–580 (1995).
    Article ADS CAS Google Scholar
  11. Cullen, P. J., Patel, Y., Kakkar, V. V., Irvine, R. F. & Authi, K. S. Biochem J. 298, 739–742 (1994).
    Article CAS Google Scholar
  12. Maekawa, M., Nakamura, S. & Hattori, S. J. biol. Chem. 268, 22948–22952 (1993).
    CAS PubMed Google Scholar
  13. Bender, A. Proc. natn. Acad. Sci. U.S.A. 90, 9926–9929 (1993).
    Article ADS CAS Google Scholar
  14. Park, H. O., Chant, J. & Herskowitz, I. Nature 365, 269–274 (1993).
    Article ADS CAS Google Scholar
  15. Fukuda, M., Aruga, J., Niinoke, M., Aimoto, S. & Mikishiba, K. J. biol. Chem. 269, 29206–29211 (1994).
    CAS PubMed Google Scholar
  16. Ramirez, M. T., Post, G. R., Sulakhe, P. V. & Brown, J. H. J. biol. Chem. 270, 8846–8451 (1995).
    Article Google Scholar
  17. Manning, S. D. & Brass, L. F. Thrombos. Haemost. 66, 393–399 (1991).
    Article CAS Google Scholar
  18. Corvazier, E. et al. Biochem. J. 281, 323–331 (1991).
    Google Scholar
  19. Hashii, M., Nozawa, Y. & Higashida, H. J. biol. Chem. 268, 19403–19410 (1993).
    CAS PubMed Google Scholar
  20. Totty, N. F., Waterfield, M. D. & Hsuan, J. J. Prot. Sci. 1, 1215–1224 (1992).
    Article CAS Google Scholar
  21. Kozak, M. Nucleic Acids Res. 15, 8125–8148 (1987).
    Article CAS Google Scholar

Download references

Author information

Authors and Affiliations

  1. Inositide Laboratory, The Babraham Institute, Babraham Hall, Cambridge, CB2 4AT, UK
    Peter J. Cullen, Andrew J. Letcher & Robin F. Irvine
  2. School of Biological Sciences, University of East Anglia, Norwich, NR4 7TJ, UK
    Peter J. Cullen & Alan P. Dawson
  3. Ludwig Institute of Cancer Research, University College London Medical School, 91 Riding House Street, London, W1P 8BT, UK
    J. Justin Hsuan & Oanh Truong
  4. The Babraham Institute, Laboratory of Molecular Signalling, Department of Zoology, University of Cambridge, Cambridge, CB2 3EJ, UK
    Trevor R. Jackson

Authors

  1. Peter J. Cullen
    You can also search for this author inPubMed Google Scholar
  2. J. Justin Hsuan
    You can also search for this author inPubMed Google Scholar
  3. Oanh Truong
    You can also search for this author inPubMed Google Scholar
  4. Andrew J. Letcher
    You can also search for this author inPubMed Google Scholar
  5. Trevor R. Jackson
    You can also search for this author inPubMed Google Scholar
  6. Alan P. Dawson
    You can also search for this author inPubMed Google Scholar
  7. Robin F. Irvine
    You can also search for this author inPubMed Google Scholar

Rights and permissions

About this article

Cite this article

Cullen, P., Hsuan, J., Truong, O. et al. Identification of a specific lns(l,3,4,5)P4-binding protein as a member of the GAP1 family.Nature 376, 527–530 (1995). https://doi.org/10.1038/376527a0

Download citation