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Regulation of fibroblast motility by the protein tyrosine phosphatase PTP-PEST.

The protein tyrosine phosphatase PTP-PEST is a cytosolic enzyme that displays a remarkable degree of selectivity for tyrosine-phosphorylated p130(Cas) as a substrate, both in vitro and in intact cells. We have investigated the physiological role of PTP-PEST using Rat1 fibroblast-derived stable cell lines that we have engineered to overexpress PTP-PEST. These cell lines exhibit normal levels of tyrosine phosphorylation of the majority of proteins but have significantly lower levels of tyrosine phosphorylation of p130(Cas) than control cells. Initial cellular events occurring following integrin-mediated attachment to fibronectin (cell attachment and spreading) are essentially unchanged in cells overexpressing PTP-PEST; similarly, the extent and time course of mitogen-activated protein kinase activation in response to integrin engagement is unchanged. In contrast, the reduced phosphorylation state of p130(Cas) is associated with a considerably reduced rate of cell migration and a failure of cells overexpressing PTP-PEST to accomplish the normally observed redistribution of p130(Cas) to the leading edge of migrating cells. Furthermore, cells overexpressing PTP-PEST demonstrate significantly reduced levels of association of p130(Cas) with the Crk adaptor protein. Our results suggest that one physiological role of PTP-PEST is to dephosphorylate p130(Cas), thereby controlling tyrosine phosphorylation-dependent signaling events downstream of p130(Cas) and regulating cell migration.

Pubmed ID: 9920935

Authors

  • Garton AJ
  • Tonks NK

Journal

The Journal of biological chemistry

Publication Data

February 5, 1999

Associated Grants

  • Agency: NCI NIH HHS, Id: CA 53840

Mesh Terms

  • Animals
  • Cell Line
  • Cell Movement
  • Crk-Associated Substrate Protein
  • Fibroblasts
  • Fibronectins
  • Phosphoproteins
  • Protein Tyrosine Phosphatase, Non-Receptor Type 12
  • Protein Tyrosine Phosphatases
  • Proteins
  • Rats
  • Retinoblastoma-Like Protein p130
  • Signal Transduction