Identification of a nucleotide exchange-promoting activity for p21ras.

  • J Downward
    Whitehead Institute for Biomedical Research, Cambridge, MA 02142.
  • R Riehl
    Whitehead Institute for Biomedical Research, Cambridge, MA 02142.
  • L Wu
    Whitehead Institute for Biomedical Research, Cambridge, MA 02142.
  • R A Weinberg
    Whitehead Institute for Biomedical Research, Cambridge, MA 02142.

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<jats:p>The biological activity of proteins encoded by the ras family of oncogenes is dependent on whether they are bound to GTP or GDP: the type of nucleotide bound is dependent on the rate of GTP hydrolysis (promoted by the GTPase-activating protein, GAP) and the rate of nucleotide exchange with cytosolic pools. A protein that stimulates the rate of exchange of guanine nucleotide on p21ras has been identified and characterized in cytoplasmic extracts of human placenta. The exchange-promoting protein runs on a gel filtration column with an apparent relative molecular weight of about 60,000. It is sensitive to heat and to trypsin. The exchange-promoting protein acts reversibly and does not cause degradation of p21ras. It is inactive towards the alpha subunit of a heterotrimeric GTP-binding protein (Go alpha) but acts on a large number of different mutant ras proteins, including transforming and effector mutants that are insensitive to the action of GAP. This protein, which we have termed REP (ras exchange-promoting), has the characteristics expected of a physiological activator of p21ras in cellular growth-signal-transduction pathways.</jats:p>

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