A cytosolic protein catalyzes the release of GDP from p21ras.
The rate of release of guanine nucleotides from the ras proteins (Ras) is extremely slow in the presence of Mg2+. It seemed likely, therefore that a factor might exist to accelerate the release of guanosine diphosphate (GDP), and hence the exchange of GDP for guanosine triphosphate (GTP). Such a factor has now been discovered in rat brain cytosol. Brain cytosol was found to catalyze, by orders of magnitude, the release of guanine nucleotides from recombinant v-H-Ras protein bound with [alpha-32P]GDP. This effect occurred even in the presence of a large excess of Mg2+, but was destroyed by heat or by incubation of the cytosol for an hour at 37 degrees C in the absence of phosphatase inhibitors. The effect was observed with either v-H-Ras or c-H-Ras, but not with p25rab3A, a small G protein with about 30% similarity to Ras. The effect could not be mimicked by addition of recombinant Ras-GAP or purified GEF, a guanine nucleotide exchange factor involved in the regulation of eukaryotic protein synthesis. By gel filtration chromatography, the factor appears to possess a molecular size between 100,000 and 160,000 daltons. This protein (Ras-guanine nucleotide-releasing factor, or Ras-GRF) may be involved in the activation of p21ras.
Wolfman
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Department of Biophysics, University of Rochester Medical Center, NY 14642.
Macara
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D000818:Animals; D001667:Binding, Competitive; D001921:Brain / Q000378:metabolism; D002793:Cholic Acids; D003600:Cytosol / Q000378:metabolism*; D006150:Guanine Nucleotides / Q000378:metabolism*; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D006153:Guanosine Diphosphate / Q000378:metabolism*; D006160:Guanosine Triphosphate / Q000031:analogs & derivatives / Q000378:metabolism; D006358:Hot Temperature; D007163:Immunosorbent Techniques; D007700:Kinetics; D015636:Magnesium Chloride / Q000494:pharmacology; D008970:Molecular Weight; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D016283:Proto-Oncogene Proteins p21(ras); D051381:Rats; D013873:Thionucleotides / Q000378:metabolism
D002793:Cholic Acids; D006150:Guanine Nucleotides; D011518:Proto-Oncogene Proteins; D013873:Thionucleotides; D015636:Magnesium Chloride; D006153:Guanosine Diphosphate; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D006160:Guanosine Triphosphate; D016283:Proto-Oncogene Proteins p21(ras); C028213:3-((3-cholamidopropyl)dimethylammonium)-1-propanesulfonate