title: Different functions of Smg GDP dissociation stimulator and mammalian counterpart of yeast Cdc25.
abstract: We have previously shown that both Smg GDP dissociation stimulator (GDS) and mammalian Cdc25 (mCdc25) stimulate the GDP/GTP exchange reaction of Ki-Ras and that Smg GDS is active only on the post-translationally lipid-modified form of Ki-Ras, whereas mCdc25 is active on both the lipid-modified and unmodified forms but is more active on the lipid-modified form. In the present study, we compared more detailed kinetic properties of Smg GDS and mCdc25 by use of the lipid-modified form of Ki-Ras as a common substrate. Both Smg GDS and mCdc25 stimulated the dissociation of GDP from Ki-Ras and formed the stable binary complex with Ki-Ras. In the presence of guanosine 5'-(3-O-thio) triphosphate (GTP gamma S), the stable ternary complex of Smg GDS-GTP gamma S-Ki-Ras was produced, whereas GTP gamma S induced the dissociation of mCdc25 from mCdc25-Ki-Ras complex, yielding GTP gamma S-Ki-Ras. mCdc25 stimulated the dissociation of GDP from both the membrane-bound and soluble forms of Ki-Ras, whereas Smg GDS was far less active on the membrane-bound form than on the soluble form. Moreover, Smg GDS translocated the GTP gamma S-bound form of membrane-bound Ki-Ras to the soluble fraction as the stable ternary complex of Smg GDS-GTP gamma S-Ki-Ras, whereas mCdc25 did not show this activity. These results suggest that Smg GDS and mCdc25 play different roles in the regulation of Ki-Ras.
authors.affiliation: Department of Biochemistry, Kobe University School of Medicine, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Nakanishi
authors.forename: K
authors.initials: K
authors.lastname: Kaibuchi
authors.forename: S
authors.initials: S
authors.lastname: Orita
authors.forename: N
authors.initials: N
authors.lastname: Ueno
authors.forename: Y
authors.initials: Y
authors.lastname: Takai
mesh_terms: D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D005656:Fungal Proteins / Q000378:metabolism*; D019204:GTP-Binding Proteins / Q000378:metabolism*; D006150:Guanine Nucleotides / Q000378:metabolism; D007700:Kinetics; D015689:Oncogene Protein p21(ras) / Q000378:metabolism; D010749:Phosphoprotein Phosphatases / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000378:metabolism*; D020668:rap GTP-Binding Proteins; D020666:ras-GRF1
chemical_list: D005656:Fungal Proteins; D006150:Guanine Nucleotides; D020666:ras-GRF1; D010749:Phosphoprotein Phosphatases; D019204:GTP-Binding Proteins; D015689:Oncogene Protein p21(ras); D020668:rap GTP-Binding Proteins