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An effector region in Eps8 is responsible for the activation of the Rac-specific GEF activity of Sos-1 and for the proper localization of the Rac-based actin–polymerizing machine

Genetic and biochemical evidence demonstrated that Eps8 is involved in the routing of signals from Ras to Rac. This is achieved through the formation of a tricomplex consisting of Eps8–E3b1–Sos-1, which is endowed with Rac guanine nucleotide exchange activity. The catalytic subunit of this complex i...

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Autores principales: Scita, Giorgio, Tenca, Pierluigi, Areces, Liliana B., Tocchetti, Arianna, Frittoli, Emanuela, Giardina, Giuseppina, Ponzanelli, Isabella, Sini, Patrizia, Innocenti, Metello, Di Fiore, Pier Paolo
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2001
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2196181/
https://www.ncbi.nlm.nih.gov/pubmed/11524436
http://dx.doi.org/10.1083/jcb.200103146
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author Scita, Giorgio
Tenca, Pierluigi
Areces, Liliana B.
Tocchetti, Arianna
Frittoli, Emanuela
Giardina, Giuseppina
Ponzanelli, Isabella
Sini, Patrizia
Innocenti, Metello
Di Fiore, Pier Paolo
author_facet Scita, Giorgio
Tenca, Pierluigi
Areces, Liliana B.
Tocchetti, Arianna
Frittoli, Emanuela
Giardina, Giuseppina
Ponzanelli, Isabella
Sini, Patrizia
Innocenti, Metello
Di Fiore, Pier Paolo
author_sort Scita, Giorgio
collection PubMed
description Genetic and biochemical evidence demonstrated that Eps8 is involved in the routing of signals from Ras to Rac. This is achieved through the formation of a tricomplex consisting of Eps8–E3b1–Sos-1, which is endowed with Rac guanine nucleotide exchange activity. The catalytic subunit of this complex is represented by Sos-1, a bifunctional molecule capable of catalyzing guanine nucleotide exchange on Ras and Rac. The mechanism by which Sos-1 activity is specifically directed toward Rac remains to be established. Here, by performing a structure–function analysis we show that the Eps8 output function resides in an effector region located within its COOH terminus. This effector region, when separated from the holoprotein, activates Rac and acts as a potent inducer of actin polymerization. In addition, it binds to Sos-1 and is able to induce Rac-specific, Sos-1–dependent guanine nucleotide exchange activity. Finally, the Eps8 effector region mediates a direct interaction of Eps8 with F-actin, dictating Eps8 cellular localization. We propose a model whereby the engagement of Eps8 in a tricomplex with E3b1 and Sos-1 facilitates the interaction of Eps8 with Sos-1 and the consequent activation of an Sos-1 Rac–specific catalytic ability. In this complex, determinants of Eps8 are responsible for the proper localization of the Rac-activating machine to sites of actin remodeling.
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spelling pubmed-21961812008-05-01 An effector region in Eps8 is responsible for the activation of the Rac-specific GEF activity of Sos-1 and for the proper localization of the Rac-based actin–polymerizing machine Scita, Giorgio Tenca, Pierluigi Areces, Liliana B. Tocchetti, Arianna Frittoli, Emanuela Giardina, Giuseppina Ponzanelli, Isabella Sini, Patrizia Innocenti, Metello Di Fiore, Pier Paolo J Cell Biol Article Genetic and biochemical evidence demonstrated that Eps8 is involved in the routing of signals from Ras to Rac. This is achieved through the formation of a tricomplex consisting of Eps8–E3b1–Sos-1, which is endowed with Rac guanine nucleotide exchange activity. The catalytic subunit of this complex is represented by Sos-1, a bifunctional molecule capable of catalyzing guanine nucleotide exchange on Ras and Rac. The mechanism by which Sos-1 activity is specifically directed toward Rac remains to be established. Here, by performing a structure–function analysis we show that the Eps8 output function resides in an effector region located within its COOH terminus. This effector region, when separated from the holoprotein, activates Rac and acts as a potent inducer of actin polymerization. In addition, it binds to Sos-1 and is able to induce Rac-specific, Sos-1–dependent guanine nucleotide exchange activity. Finally, the Eps8 effector region mediates a direct interaction of Eps8 with F-actin, dictating Eps8 cellular localization. We propose a model whereby the engagement of Eps8 in a tricomplex with E3b1 and Sos-1 facilitates the interaction of Eps8 with Sos-1 and the consequent activation of an Sos-1 Rac–specific catalytic ability. In this complex, determinants of Eps8 are responsible for the proper localization of the Rac-activating machine to sites of actin remodeling. The Rockefeller University Press 2001-09-03 /pmc/articles/PMC2196181/ /pubmed/11524436 http://dx.doi.org/10.1083/jcb.200103146 Text en Copyright © 2001, The Rockefeller University Press This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/).
spellingShingle Article
Scita, Giorgio
Tenca, Pierluigi
Areces, Liliana B.
Tocchetti, Arianna
Frittoli, Emanuela
Giardina, Giuseppina
Ponzanelli, Isabella
Sini, Patrizia
Innocenti, Metello
Di Fiore, Pier Paolo
An effector region in Eps8 is responsible for the activation of the Rac-specific GEF activity of Sos-1 and for the proper localization of the Rac-based actin–polymerizing machine
title An effector region in Eps8 is responsible for the activation of the Rac-specific GEF activity of Sos-1 and for the proper localization of the Rac-based actin–polymerizing machine
title_full An effector region in Eps8 is responsible for the activation of the Rac-specific GEF activity of Sos-1 and for the proper localization of the Rac-based actin–polymerizing machine
title_fullStr An effector region in Eps8 is responsible for the activation of the Rac-specific GEF activity of Sos-1 and for the proper localization of the Rac-based actin–polymerizing machine
title_full_unstemmed An effector region in Eps8 is responsible for the activation of the Rac-specific GEF activity of Sos-1 and for the proper localization of the Rac-based actin–polymerizing machine
title_short An effector region in Eps8 is responsible for the activation of the Rac-specific GEF activity of Sos-1 and for the proper localization of the Rac-based actin–polymerizing machine
title_sort effector region in eps8 is responsible for the activation of the rac-specific gef activity of sos-1 and for the proper localization of the rac-based actin–polymerizing machine
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2196181/
https://www.ncbi.nlm.nih.gov/pubmed/11524436
http://dx.doi.org/10.1083/jcb.200103146
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