title: Spatiotemporal organization of Ras signaling: rasosomes and the galectin switch.
abstract: 1. Ras signaling and oncogenesis depend on the dynamic interplay of Ras with distinctive plasma membrane (PM) microdomains and various intracellular compartments. Such interaction is dictated by individual elements in the carboxy-terminal domain of the Ras proteins, including a farnesyl isoprenoid group, sequences in the hypervariable region (hvr)-linker, and palmitoyl groups in H/N-Ras isoforms. 2. The farnesyl group acts as a specific recognition unit that interacts with prenyl-binding pockets in galectin-1 (Gal-1), galectin-3 (Gal-3), and cGMP phosphodiesterase delta. This interaction appears to contribute to the prolongation of Ras signals in the PM, the determination of Ras effector usage, and perhaps also the transport of cytoplasmic Ras. Gal-1 promotes H-Ras signaling to Raf at the expense of phosphoinositide 3-kinase (PI3-K) and Ral guanine nucleotide exchange factor (RalGEF), while galectin-3 promotes K-Ras signaling to both Raf and PI3-K. 3. The hvr-linker and the palmitates of H-Ras and N-Ras determine the micro- and macro-localizations of these proteins in the PM and in the Golgi, as well as in 'rasosomes', randomly moving nanoparticles that carry palmitoylated Ras proteins and their signal through the cytoplasm.4. The dynamic compartmentalization of Ras proteins contributes to the spatial organization of Ras signaling, promotes redistribution of Ras, and provides an additional level of selectivity to the signal output of this regulatory GTPase.
authors.affiliation: Department of Neurobiochemistry, George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Uri
authors.initials: U
authors.lastname: Ashery
authors.forename: Ofer
authors.initials: O
authors.lastname: Yizhar
authors.forename: Barak
authors.initials: B
authors.lastname: Rotblat
authors.forename: Galit
authors.initials: G
authors.lastname: Elad-Sfadia
authors.forename: Batya
authors.initials: B
authors.lastname: Barkan
authors.forename: Roni
authors.initials: R
authors.lastname: Haklai
authors.forename: Yoel
authors.initials: Y
authors.lastname: Kloog
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D019556:COS Cells; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D037483:Galectin 1 / Q000737:chemistry / Q000502:physiology*; D037502:Galectin 3 / Q000737:chemistry / Q000502:physiology*; D006801:Humans; D021962:Membrane Microdomains / Q000378:metabolism; D008954:Models, Biological; D008958:Models, Molecular; D008969:Molecular Sequence Data; D017434:Protein Structure, Tertiary; D021381:Protein Transport; D051381:Rats; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction; D018631:ras Proteins / Q000737:chemistry* / Q000378:metabolism*
chemical_list: D037483:Galectin 1; D037502:Galectin 3; D018631:ras Proteins