PREL1 provides a link from Ras signalling to the actin cytoskeleton via Ena/VASP proteins

Ena/VASP family proteins are important modulators of cell migration and localize to focal adhesions, stress fibres and the very tips of lamellipodia and filopodia. Proline-rich proteins like vinculin and zyxin are well established interaction partners, which mediate Ena/VASP-recruitment via their EVH1-domains to focal adhesions and stress fibres. However, it is still unclear, which binding partners Ena/VASP proteins may have at lamellipodia tips and how their recruitment to these cellular protrusions is regulated. Here, we report the identification of a novel protein with high similarity to the C elegans MIG-10 protein, which we termed PRELI (Proline Rich EVH1 Ligand). PRELI is a 74 kDa protein and shares homology with the Grb7-family of signalling adaptors. We show that PRELI directly binds to Ena/VASP proteins and co-localizes with them at lamellipodia tips and at focal adhesions in response to Ras activation. Moreover, PRELI directly binds to activated Ras in a phosphoinositide-dependent manner. Thus, our data pinpoint PRELI as the first direct link between Ras signalling and cytoskeletal remodelling via Ena/VASP proteins during cell migration and spreading. (C) 2004 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.