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Differential regulation of rasGAP and neurofibromatosis gene product activities

Abstract

THE ras-encoded p21ras proteins bind GTP very tightly, but catalyse hydrolysis to GDP very slowly1. In humans, two genes encode proteins that stimulate this GTPase activity (GAP, or GTPase-activating proteins)2, one of relative molecular mass 120,000, referred to as p120-GAP, and another NF1-GAP, which is encoded by the neurofibromatosis type-1 gene3–5. Both GAPs are widely expressed in mammalian tissues6,7. Here we show that although they will both bind oncogenic mutants of p21ras, neither will stimulate their GTPase activity. NF1-GAP binds to the p21ras proteins up to 300 times more efficiently than p120-GAP. The two GAPs are inhibited to different extents by certain lipids: micromolar concentrations of arachidonate, phosphatidate and phosphatidyIinositol-4,5-bisphosphate affect only NF1-GAP. This inhibition does not compete with p21ras, and lipid-inactivated NF1-G AP can still bind p21ras. We used the detergent dodecyl maltoside, which inhibits only NF1-GAP, to distinguish between the two activities in cell extracts and found both types present together in several mammalian cell lines. In contrast, GAP activity in extracts of Xenopus oocytes was not affected by dodecyl maltoside. By these criteria, the mammalian cells contain both GAP activities and the oocytes have only p120-like GAP activity. These results indicate that more than one GAP regulates p21ras in the same cell.

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References

  1. Barbacid, M. A. Rev. Biochem. 56, 779–827 (1987).

    CAS  Article  Google Scholar 

  2. McCormick, F. Oncogene 5, 1281–1283 (1990).

    CAS  PubMed  Google Scholar 

  3. Martin, G. A. et al. Cell 63, 843–849 (1990).

    CAS  Article  PubMed  Google Scholar 

  4. Xu, G. et al. Cell 63, 835–841 (1990).

    CAS  Article  PubMed  Google Scholar 

  5. Ballester, R. et al. Cell 63, 851–859 (1990).

    CAS  Article  PubMed  Google Scholar 

  6. Trahey, M. et al. Science 242, 1697–1700 (1988).

    ADS  CAS  Article  PubMed  Google Scholar 

  7. Buchberg, A. M., Cleveland, L. S., Jenkins, N. A. & Copeland, N. G. Nature 347, 291–294 (1990).

    ADS  CAS  Article  PubMed  Google Scholar 

  8. Trahey, M. & McCormick, F. Science 238, 542–545 (1987).

    ADS  CAS  Article  PubMed  Google Scholar 

  9. Adari, H., Lowy, D. R., Willumsen, B. M., Der, C. J. & McCormick, F. Science 240, 518–521 (1988).

    ADS  CAS  Article  PubMed  Google Scholar 

  10. Calés, C. Hancock, J. F., Marshall, C. J. & Hall, A. Nature 332, 548–551 (1988).

    ADS  Article  PubMed  Google Scholar 

  11. Vogel, U. S. et al. Nature 335, 90–93 (1988).

    ADS  CAS  Article  PubMed  Google Scholar 

  12. Yatani, A. et al. Cell 61, 769–776 (1990).

    CAS  Article  PubMed  Google Scholar 

  13. Bourne, H. R., Sanders, D. A. & McCormick, F. Nature 349, 117–127 (1991).

    ADS  CAS  Article  PubMed  Google Scholar 

  14. Tsai, M.-H., Yu, C.-L., Wei, F. S. & Stacey, D. W. Science 243, 522–526 (1989).

    ADS  CAS  Article  PubMed  Google Scholar 

  15. Tsai, M.-H., Hall, A. & Stacey, D. W. Molec. cell. Biol. 9, 5260–5264 (1989).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  16. Yu, C.-L., Tsai, M.-H. & Stacey, D. W. Molec. cell. Biol. 10, 6683–6689 (1990).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  17. Downward, J., Graves, J. D., Warne, P. H., Rayter, S. & Cantrell, D. A. Nature 346, 719–723 (1990).

    ADS  CAS  Article  PubMed  Google Scholar 

  18. Goldschmidt-Clermont, P. J., Machesky, L. M., Baldassare, J. J. & Pollard, T. D. Science 247, 1575–1578 (1990).

    ADS  CAS  Article  PubMed  Google Scholar 

  19. Birchmeier, C., Broek, D. & Wigler, M. Cell 43, 615–621 (1985).

    CAS  Article  PubMed  Google Scholar 

  20. Tanaka, K. et al. Molec. cell. Biol. 10, 4303–4313 (1990).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  21. Tanaka, K., Lin, B. K., Wood, D. R. & Tamanoi, F. Proc. natn. Acad. Sci. U.S.A. 88, 468–472 (1991).

    ADS  CAS  Article  Google Scholar 

  22. Zhang, K. et al. Nature 346, 754–756 (1990).

    ADS  CAS  Article  PubMed  Google Scholar 

  23. Shacter, E. Analyt. Biochem. 138, 416–420 (1984).

    CAS  Article  PubMed  Google Scholar 

  24. Furth, M. E., Davis, L. J., Fleurdelys, B. & Scolnick, E. M. J. Virol. 43, 294–304 (1982).

    CAS  PubMed  PubMed Central  Google Scholar 

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Bollag, G., McCormick, F. Differential regulation of rasGAP and neurofibromatosis gene product activities. Nature 351, 576–579 (1991). https://doi.org/10.1038/351576a0

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