A new function of p120-GTPase-activating protein. Prevention of the guanine nucleotide exchange factor-stimulated nucleotide exchange on the active form of Ha-ras p21.

The Journal of Biological Chemistry
C GiglioneA Parmeggiani


This work studies the coordination of the action of GTPase-activating protein (GAP) and guanine nucleotide exchange factor (GEF) on activated human c-Ha-Ras p21. Purified human p120-GAP was obtained with a new efficient procedure. To distinguish the GTPase-activating effect of p120-GAP from other effects dependent on the interaction with activated Ha-Ras, the nonhydrolyzable GTP analogue guanosine 5'-O-(thiotriphosphate) (GTPgammaS) was used. The results showed that the GTPgammaS/GTPgammaS exchange enhanced by the C-terminal catalytic domain of the yeast GEF Sdc25p (C-Sdc25p) is prevented by p120-GAP. This effect is strictly specific for the activated form of Ha-Ras, the target of GAP; no effect on Ha-Ras.GDP was detectable. The GAP catalytic domain also inhibited C-Sdc25p but to a lower extent. The interfering effect by p120-GAP was also evident in a homologous mammalian system, using full-length mouse RasGEF, its C-terminal half-molecule, or C-terminal catalytic domain. As a consequence of this inhibition, presence of p120-GAP enhanced the regeneration of Ha-Ras.GTPgammaS by GEF at a GDP:GTPgammaS ratio mimicking the in vivo GDP:GTP ratio. Our work describes a novel function of p120-GAP and suggests a mechanism by which GAP p...Continue Reading


Dec 1, 1992·Molecular Biology of the Cell·M S Nur-E-Kamal, H Maruta
Mar 1, 1992·Molecular Microbiology·A WeijlandA Parmeggiani
Aug 23, 1990·Nature·J DownwardD A Cantrell
Jan 1, 1989·Proteins·M D SchaberJ B Gibbs
Aug 1, 1995·FEBS Letters·A Wittinghofer, C Herrmann
Feb 14, 1995·Proceedings of the National Academy of Sciences of the United States of America·J S ScheeleG R Boss
Feb 15, 1995·European Journal of Biochemistry·M SegalA Levitzki
Jul 1, 1993·Trends in Biochemical Sciences·M S Marshall
Dec 16, 1993·Nature·M S Boguski, F McCormick
Mar 29, 1993·FEBS Letters·P F StoutenA Valencia
Jun 15, 1993·Proceedings of the National Academy of Sciences of the United States of America·M SegalA Levitzki
May 10, 1996·The Journal of Biological Chemistry·L A QuilliamC J Der
Jul 19, 1996·The Journal of Biological Chemistry·J B CréchetA Parmeggiani

❮ Previous
Next ❯


Aug 12, 1998·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·J Y Pan, M Wessling-Resnick
Apr 26, 2008·Molecular BioSystems·Shintaro Iwashita, Si-Young Song
Oct 29, 1999·European Journal of Biochemistry·I RubioR Wetzker
Jul 10, 2010·Journal of Biomedicine & Biotechnology·Sylwia JancíkMarián Hajdúch
Apr 2, 2019·Nucleosides, Nucleotides & Nucleic Acids·Ninticha ThavoncharoensubYosuke Taniguchi

❮ Previous
Next ❯

Related Concepts

Related Feeds

ASBMB Publications

The American Society for Biochemistry and Molecular Biology (ASBMB) includes the Journal of Biological Chemistry, Molecular & Cellular Proteomics, and the Journal of Lipid Research. Discover the latest research from ASBMB here.