HD-PTP inhibits endothelial migration through its interaction with Src

Massimo Mariotti, Sara Castiglioni, Jose M. Garcia-Manteiga, Laura Beguinot, Jeanette A M Maier

Research output: Contribution to journalArticle

Abstract

Endothelial migration, early step in angiogenesis, is tightly regulated by the coordinated action of tyrosine kinases and tyrosine phosphatases. HD-PTP contributes to endothelial motility, since endothelial cells silencing HD-PTP after transfection with iRNA acquire a scattered and spindle-shaped phenotype and migrate faster than controls. Since (i) the proto-oncogene Src contributes to the regulation of cell motility and (ii) HD-PTP has a potential binding site for Src, we investigated whether an interplay exists between these two proteins. We found that Src binds HD-PTP and this interaction is enhanced after exposure to basic fibroblast growth factor. While HD-PTP does not modulate the levels of Src phosphorylation both in vitro and in vivo, we found that Src phosphorylates HD-PTP on tyrosine residues. Here we show for the first time that (i) HD-PTP has a tyrosine phosphatase activity; (ii) HD-PTP phosphorylation by Src inhibits its enzymatic activity. Interestingly, pharmacological and genetic inhibition of Src abrogates the migratory phenotype of endothelial cells silencing HD-PTP. On these bases, and because we have previously demonstrated that HD-PTP binds and dephosphorylates focal adhesion kinase (FAK), another crucial regulator of cell migration, we hypothesize that HD-PTP participates to the regulation of endothelial motility through its interactions with Src and FAK.

Original languageEnglish
Pages (from-to)687-693
Number of pages7
JournalInternational Journal of Biochemistry and Cell Biology
Volume41
Issue number3
DOIs
Publication statusPublished - Mar 2009

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Tyrosine
Focal Adhesion Protein-Tyrosine Kinases
Phosphorylation
Endothelial cells
Phosphoric Monoester Hydrolases
Cell Movement
Endothelial Cells
Phenotype
Proto-Oncogenes
Fibroblast Growth Factor 2
Protein-Tyrosine Kinases
Transfection
Binding Sites
Cells
Pharmacology
Proteins
In Vitro Techniques

Keywords

  • Cell migration
  • Endothelial
  • FAK
  • HD-PTP
  • Src

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology

Cite this

HD-PTP inhibits endothelial migration through its interaction with Src. / Mariotti, Massimo; Castiglioni, Sara; Garcia-Manteiga, Jose M.; Beguinot, Laura; Maier, Jeanette A M.

In: International Journal of Biochemistry and Cell Biology, Vol. 41, No. 3, 03.2009, p. 687-693.

Research output: Contribution to journalArticle

Mariotti, Massimo ; Castiglioni, Sara ; Garcia-Manteiga, Jose M. ; Beguinot, Laura ; Maier, Jeanette A M. / HD-PTP inhibits endothelial migration through its interaction with Src. In: International Journal of Biochemistry and Cell Biology. 2009 ; Vol. 41, No. 3. pp. 687-693.
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