EPS8 and E3B1 transduce signals from Ras to Rac

Giorgio Scita, Johan Nordstrom, Roberta Carbone, Pierluigi Tenca, Gluseppina Giardina, Silvio Gutkind, Mattias Bjarnegård, Christer Betsholtz, Pier Paolo Di Fiore

Research output: Contribution to journalArticlepeer-review

Abstract

The small guanine nucleotide (GTP)-binding protein Rac regulates mitogen-induced cytoskeletal changes and c-Jun amino-terminal kinase (JNK), and its activity is required for Ras-mediated cell transformation. Epistatic analysis placed Rac as a key downstream target in Ras signalling; however, the biochemical mechanism regulating the cross-talk among these small GTP- binding proteins remains to be elucidated. Eps8 (relative molecular mass 97,000) is a substrate of receptors with tyrosine kinase activity which binds, through its SH3 domain, to a protein designated E3b1/Abi-1 (refs 4, 5). Here we show that Eps8 and E3b1/Abi-1 participate in the transduction of signals from Ras to Rac, by regulating Rac-specific guanine nucleotide exchange factor (GEF) activities. We also show that Eps8, E3b1 and Sos-1 form a tri-complex in vivo that exhibits Rac-specific GEF activity in vitro. We propose a model in which Eps8 mediates the transfer of signals between Ras and Rac, by forming a complex with E3b1 and Sos-1.

Original languageEnglish
Pages (from-to)290-293
Number of pages4
JournalNature
Volume401
Issue number6750
DOIs
Publication statusPublished - Sep 16 1999

ASJC Scopus subject areas

  • General

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