title: Post-translational modifications of Ras and Ral are important for the action of Ral GDP dissociation stimulator.
abstract: Ral GDP dissociation stimulator (RalGDS) is a GDP/GTP exchange protein of Ral and a new effector protein of Ras. Therefore, there may be a new signaling pathway from Ras to Ral. In this paper, we examined the roles of the post-translational modifications of Ras and Ral on this new signal transduction pathway. The post-translationally modified form of Ras bound to RalGDS more effectively than the unmodified form. The modification of Ras was required to regulate the distribution of RalGDS between the cytosol and membrane fractions in COS cells. The post-translational modification of Ral enhanced the activities of RalGDS to stimulate the dissociation of GDP from and the binding of GTP to Ral. Furthermore, the modified form of Ral bound to Ral-binding protein 1 (RalBP1), a putative effector protein of Ral, more effectively than the unmodified form. Taken together with the observations that Ras and Ral are localized to the membranes, these results suggest that the post-translational modifications of Ras and Ral play a role for transmitting the signal effectively on the membranes in the signal transduction pathway of Ras/RalGDS/Ral/RalBP1.
authors.affiliation: Department of Biochemistry, Hiroshima University School of Medicine, 1-2-3 Kasumi, Minami-ku, Hiroshima 734, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Hinoi
authors.forename: S
authors.initials: S
authors.lastname: Kishida
authors.forename: S
authors.initials: S
authors.lastname: Koyama
authors.forename: M
authors.initials: M
authors.lastname: Ikeda
authors.forename: Y
authors.initials: Y
authors.lastname: Matsuura
authors.forename: A
authors.initials: A
authors.lastname: Kikuchi
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism; D002451:Cell Compartmentation; D002462:Cell Membrane / Q000378:metabolism; D002522:Chlorocebus aethiops; D005656:Fungal Proteins / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000378:metabolism*; D020690:GTPase-Activating Proteins; D046911:Macromolecular Substances; D008969:Molecular Sequence Data; D017354:Point Mutation; D011485:Protein Binding; D011499:Protein Processing, Post-Translational; D016283:Proto-Oncogene Proteins p21(ras) / Q000378:metabolism*; D011994:Recombinant Proteins; D015398:Signal Transduction; D013329:Structure-Activity Relationship; D020725:ral GTP-Binding Proteins; D020726:ral Guanine Nucleotide Exchange Factor; D020668:rap GTP-Binding Proteins
chemical_list: D002352:Carrier Proteins; D005656:Fungal Proteins; D020690:GTPase-Activating Proteins; D046911:Macromolecular Substances; C094755:Ralbp1 protein, rat; D011994:Recombinant Proteins; D020726:ral Guanine Nucleotide Exchange Factor; D019204:GTP-Binding Proteins; D016283:Proto-Oncogene Proteins p21(ras); D020725:ral GTP-Binding Proteins; D020668:rap GTP-Binding Proteins