Phosphorylation-dependent paxillin-ERK association mediates hepatocyte growth factor-stimulated epithelial morphogenesis

Mol Cell. 2003 Nov;12(5):1275-85. doi: 10.1016/s1097-2765(03)00406-4.


Activation of the hepatocyte growth factor (HGF) receptor c-met results in the regulation of cell-matrix interactions, including the MAPK-dependent stimulation of epithelial cell morphogenesis. In the present study we demonstrate that HGF stimulates the localization of ERK to sites of cell-matrix interactions and that this is mediated by the tyrosine phosphorylation-dependent association of inactive ERK and the focal adhesion complex protein paxillin. In addition, paxillin was found to associate with the upstream MAP kinases Raf and MEK, resulting in a complex that can mediate localized ERK activation. Mutation of the ERK binding site in paxillin prevented HGF-stimulated ERK-paxillin association and eliminated HGF-induced cell spreading and branching process formation. These experiments reveal that paxillin-dependent ERK activation at sites of cell-matrix interaction is critical for HGF-stimulated epithelial morphogenesis.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Cell Line
  • Cytoskeletal Proteins / genetics
  • Cytoskeletal Proteins / metabolism*
  • Enzyme Activation
  • Epithelial Cells / physiology*
  • Hepatocyte Growth Factor / metabolism*
  • Mice
  • Mitogen-Activated Protein Kinase Kinases / metabolism
  • Mitogen-Activated Protein Kinases / metabolism*
  • Morphogenesis / physiology*
  • Multienzyme Complexes
  • Mutagenesis, Site-Directed
  • Paxillin
  • Phosphoproteins / genetics
  • Phosphoproteins / metabolism*
  • Phosphorylation
  • Proto-Oncogene Proteins c-raf / metabolism
  • RNA Interference
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism
  • src-Family Kinases / metabolism


  • Cytoskeletal Proteins
  • Multienzyme Complexes
  • Paxillin
  • Phosphoproteins
  • Pxn protein, mouse
  • Recombinant Fusion Proteins
  • Hepatocyte Growth Factor
  • src-Family Kinases
  • Proto-Oncogene Proteins c-raf
  • Mitogen-Activated Protein Kinases
  • Mitogen-Activated Protein Kinase Kinases