PMID:14636584

Citation	Ishibe, S, Joly, D, Zhu, X and Cantley, LG (2003) Phosphorylation-dependent paxillin-ERK association mediates hepatocyte growth factor-stimulated epithelial morphogenesis. Mol. Cell 12:1275-85
Abstract	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.
Links	PubMed
Keywords	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
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