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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...
Autores principales: | , , , , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
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The Rockefeller University Press
2001
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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. |
format | Text |
id | pubmed-2196181 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2001 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
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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