title: Impaired c-src activation and motility defects in PEA3-null fibroblasts.
abstract: Null mutations in the pea3 allele compromise the capacity of mammary tumors to metastasize in MMTV-Neu/ErbB2/HER2 transgenic mice, indicating a motility defect in PEA3-null cells. Cellular and biochemical analyses of established PEA3-null fibroblasts show impaired motility and aberrant localization of adhesion proteins in spreading cells. Our results show that PEA3-/- cells express normal levels of key adhesion components, but that spreading PEA3-null cells fail to activate c-src and to downregulate phospho-FAK(Y397), suggesting that focal adhesion signaling is impaired. Supporting this, biochemical analysis revealed that adhesion complex-associated proteins such as p130Cas failed to undergo tyrosine phosphorylation and dissociated from the adhesion complex with delayed kinetics. Overall our data show that the motility defects observed in PEA3-null cells are due to altered adhesion signaling.
authors.affiliation: Department of Cellular and Molecular Medicine, University of Ottawa, 451 Smyth Rd, Ottawa, ON, Canada K1H8M5.
authors.forename: Ziad Y
authors.initials: ZY
authors.lastname: Chaar
authors.forename: Laura
authors.initials: L
authors.lastname: Hastings
authors.forename: Roshan
authors.initials: R
authors.lastname: Sriram
authors.forename: Marlene
authors.initials: M
authors.lastname: McKay
authors.forename: Lilia
authors.initials: L
authors.lastname: Antonova
authors.forename: John A
authors.initials: JA
authors.lastname: Hassell
authors.forename: Luc A
authors.initials: LA
authors.lastname: Sabourin
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002465:Cell Movement / Q000502:physiology*; D002478:Cells, Cultured; D050719:Crk-Associated Substrate Protein / Q000378:metabolism*; D004622:Embryo, Mammalian / Q000166:cytology / Q000378:metabolism; D005260:Female; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism*; D005353:Fibronectins / Q000494:pharmacology; D005455:Fluorescent Antibody Technique; D022001:Focal Adhesions / Q000502:physiology; D016391:Genes, src / Q000502:physiology*; D047468:Immunoprecipitation; D008324:Mammary Tumor Virus, Mouse / Q000235:genetics; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D010766:Phosphorylation; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics; D015398:Signal Transduction; D014157:Transcription Factors / Q000502:physiology*; D014443:Tyrosine / Q000378:metabolism
chemical_list: D050719:Crk-Associated Substrate Protein; D005353:Fibronectins; D018719:Erb-b2 Receptor Tyrosine Kinases; D014157:Transcription Factors; D014443:Tyrosine; C493842:Bcar1 protein, mouse; C065788:transcription factor PEA3