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

Citation
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
Citations number
36
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Cell & Developmental Biology
Journal title
JOURNAL OF CELL BIOLOGY
ISSN journal
0021-9525 → ACNP
Volume
154
Issue
5
Year of publication
2001
Pages
1031 - 1044
Database
ISI
SICI code
0021-9525(20010903)154:5<1031:AERIEI>2.0.ZU;2-J
Abstract
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 gu anine nucleotide exchange activity. The catalytic subunit of this complex i s represented by Sos-1, a bifunctional molecule capable of catalyzing guani ne nucleoticle exchange on Ras and Rac. The mechanism by which Sos-1 activi ty is specifically directed toward Rac remains to be established. Here, by performing a structure-function analysis we show that the Eps8 output funct ion resides in an effector region located within its COOH terminus. This ef fector 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 exc hange activity. Finally, the Eps8 effector-region mediates a direct interac tion 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 activati on of an Sos-1 Rac-specific catalytic ability. In this complex, determinant s of Eps8 are responsible for the proper localization of the Rac-activating machine to sites of actin remodeling.