title: Exchange factors of the RasGRP family mediate Ras activation in the Golgi.
abstract: H-Ras and N-Ras become activated both at the plasma membrane and in endomembrane structures such as the Golgi apparatus. This compartmentalized activation is relevant from a signaling standpoint, because effector molecules can become activated differently depending on the region of the cell where Ras proteins are activated. An unsolved question in this new regulatory mechanism is the understanding of how Ras proteins become activated in endomembranes. To approach this problem, we have studied the subcellular distribution and activities of a number of Ras guanosine nucleotide exchange factors. Our results indicate that Ras activation at the plasma membrane and endoplasmic reticulum is an unspecific process that can be achieved by most Ras activators. In contrast, GTP loading of Ras at the Golgi is only induced by members of the Ras guanosine nucleotide releasing protein family. In agreement with these observations, Ras guanosine nucleotide releasing proteins are the only Ras activators showing localization in the Golgi. These results indicate that the compartmentalized activation of effector pathways by Ras proteins depends not only on the specific localization of the GTPases but also in the availability of GDP/GTP exchange factors capable of activating Ras proteins in specific subcellular compartments.
authors.affiliation: Centro de Investigación del Cáncer and Instituto de Biología Molecular y Celular del Cáncer, University of Salamanca, Consejo Superior de Investigaciones Científicas, Campus Unamuno, E-37007 Salamanca, Spain.
authors.forename: Maria J
authors.initials: MJ
authors.lastname: Caloca
authors.forename: José L
authors.initials: JL
authors.lastname: Zugaza
authors.forename: Xosé R
authors.initials: XR
authors.lastname: Bustelo
mesh_terms: D016475:3T3 Cells; D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D019556:COS Cells; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology*; D004721:Endoplasmic Reticulum / Q000378:metabolism; D005822:Genetic Vectors; D006056:Golgi Apparatus / Q000378:metabolism*; D020662:Guanine Nucleotide Exchange Factors; D006160:Guanosine Triphosphate / Q000378:metabolism; D051379:Mice; D008856:Microscopy, Fluorescence; D008969:Molecular Sequence Data; D010957:Plasmids / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction; D014162:Transfection; D016335:Zinc Fingers; D018631:ras Proteins / Q000378:metabolism*
chemical_list: D004268:DNA-Binding Proteins; D020662:Guanine Nucleotide Exchange Factors; C112278:Rasgrp1 protein, mouse; D006160:Guanosine Triphosphate; D018631:ras Proteins