Eps8 in the midst of GTPases

Pier Paolo Di Fiore, Giorgio Scita

Research output: Contribution to journalArticle

Abstract

Eps8, originally identified as a substrate for the kinase activity of the epidermal growth factor receptor (EGFR), displays a domain organization typical of a signaling molecule that includes a putative N-terminal PTB domain, a central SH3 domain, and a C-terminal "effector region". This latter region directs Eps8 localization within the cell and is sufficient to activate the GTPase, Rac, leading to actin cytoskeletal remodeling. Eps8 binds, through its SH3 domain, to either Abi1 (also called E3b1) or RN-tre. Abi1 scaffolds together Eps8 and Sos1, a dual specificity guanine nucleotide exchange factor for Ras and Rac proteins, thus facilitating the formation of a trimeric complex, in turn required for activation of Rac. On the other hand, RN-tre, a Rab5 GTPase activating protein, by entering in a complex with Eps8, inhibits EGFR internalization. Furthermore, RN-tre competes with Abi1 for binding to Eps8, diverting the latter from its Rac-activating function. Thus, depending on its engagement in different complexes, Eps8 participates to EGFR signaling through Rac and endocytosis through Rab5.

Original languageEnglish
Pages (from-to)1178-1183
Number of pages6
JournalInternational Journal of Biochemistry and Cell Biology
Volume34
Issue number10
DOIs
Publication statusPublished - 2002

Keywords

  • EGFR
  • Eps8
  • Rab5
  • Rac

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology

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