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

FEBS Lett. 2005 Jan 17;579(2):455-63. doi: 10.1016/j.febslet.2004.10.110.


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 PREL1 (Proline Rich EVH1 Ligand). PREL1 is a 74 kDa protein and shares homology with the Grb7-family of signalling adaptors. We show that PREL1 directly binds to Ena/VASP proteins and co-localizes with them at lamellipodia tips and at focal adhesions in response to Ras activation. Moreover, PREL1 directly binds to activated Ras in a phosphoinositide-dependent manner. Thus, our data pinpoint PREL1 as the first direct link between Ras signalling and cytoskeletal remodelling via Ena/VASP proteins during cell migration and spreading.

Publication types

  • Duplicate Publication
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actin Cytoskeleton / immunology
  • Actin Cytoskeleton / metabolism*
  • Actins / metabolism
  • Adaptor Proteins, Signal Transducing / analysis
  • Adaptor Proteins, Signal Transducing / immunology
  • Adaptor Proteins, Signal Transducing / metabolism*
  • Animals
  • Antibodies, Monoclonal / immunology
  • Biological Assay
  • Cell Adhesion
  • Cell Adhesion Molecules / metabolism*
  • Cell Line
  • Cell Movement / physiology
  • Cytoskeletal Proteins
  • DNA-Binding Proteins / immunology
  • DNA-Binding Proteins / metabolism*
  • Fibroblasts / chemistry
  • Fibronectins / chemistry
  • Glycoproteins / immunology
  • Humans
  • Immunoprecipitation
  • Membrane Proteins
  • Mice
  • Microfilament Proteins / metabolism*
  • Phosphoproteins / metabolism*
  • Pseudopodia / chemistry
  • Pseudopodia / physiology
  • Signal Transduction
  • Vinculin / immunology
  • Zyxin
  • ras Proteins / metabolism*


  • APBB1IP protein, human
  • Actins
  • Adaptor Proteins, Signal Transducing
  • Antibodies, Monoclonal
  • Cell Adhesion Molecules
  • Cytoskeletal Proteins
  • DNA-Binding Proteins
  • ENA-VASP proteins
  • Fibronectins
  • Glycoproteins
  • Membrane Proteins
  • Microfilament Proteins
  • Phosphoproteins
  • ZYX protein, human
  • Zyxin
  • vasodilator-stimulated phosphoprotein
  • Vinculin
  • ras Proteins