Eps8 in the midst of GTPases.
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.
Department of Experimental Oncology, European Institute of Oncology, Via Ripamonti, 435, 20141 Milan, Italy. gscita@ieo.it
Pier Paolo
PP
Di Fiore
Giorgio
G
Scita
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D003598:Cytoskeletal Proteins; D020558:GTP Phosphohydrolases / Q000378:metabolism*; D051379:Mice; D014176:Protein Biosynthesis; D011487:Protein Conformation; D011506:Proteins / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*; D015398:Signal Transduction
D048868:Adaptor Proteins, Signal Transducing; D003598:Cytoskeletal Proteins; C083430:Eps8 protein, mouse; D011506:Proteins; D020558:GTP Phosphohydrolases