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Titolo:
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
Autore:
Scita, G; Tenca, P; Areces, LB; Tocchetti, A; Frittoli, E; Giardina, G; Ponzanelli, I; Sini, P; Innocenti, M; Di Fiore, PP;
Indirizzi:
European Inst Oncol, Dept Expt Oncol, I-20141 Milan, Italy European Inst Oncol Milan Italy I-20141 Expt Oncol, I-20141 Milan, Italy Firc Inst Mol Oncol, I-20134 Milan, Italy Firc Inst Mol Oncol Milan Italy I-20134 Mol Oncol, I-20134 Milan, Italy Univ Milan, Dept Med Surg & Odontoiatry, I-20122 Milan, Italy Univ Milan Milan Italy I-20122 Surg & Odontoiatry, I-20122 Milan, Italy
Titolo Testata:
JOURNAL OF CELL BIOLOGY
fascicolo: 5, volume: 154, anno: 2001,
pagine: 1031 - 1044
SICI:
0021-9525(20010903)154:5<1031:AERIEI>2.0.ZU;2-J
Fonte:
ISI
Lingua:
ENG
Soggetto:
FILAMENT-BINDING PROTEIN; ARP2/3 COMPLEX; GUANOSINE TRIPHOSPHATASES; TRANSFORMING ACTIVITY; ADHERENS JUNCTION; FAMILY PROTEINS; VAV FAMILY; F-ACTIN; GROWTH; SIGNALS;
Keywords:
Eps8; Rac; Sos-1; cytoskeleton; GEF;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
36
Recensione:
Indirizzi per estratti:
Indirizzo: Di Fiore, PP European Inst Oncol, Dept Expt Oncol, Via Ripamonti 435, I-20141 Milan, Italy European Inst Oncol Via Ripamonti 435 Milan Italy I-20141ly
Citazione:
G. Scita et al., "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", J CELL BIOL, 154(5), 2001, pp. 1031-1044

Abstract

Genetic and biochemical evidence demonstrated that Eps8 is involved in therouting of signals from Ras to Rac. This is achieved through the formationof 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 nucleoticle exchange on Ras and Rac. The mechanism by which Sos-1 activity is specifically directed toward Rac remains to be established. Here, byperforming 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 actsas 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.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 27/09/20 alle ore 12:51:35