Impaired c-src activation and motility defects in PEA3-null fibroblasts Academic Article uri icon

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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

  • Chaar, Ziad Y
  • Hastings, Laura
  • Sriram, Roshan
  • McKay, Marlene
  • Antonova, Lilia
  • Hassell, John Algernon
  • Sabourin, Luc A

publication date

  • December 2012

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