title: HD-PTP inhibits endothelial migration through its interaction with Src.
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.
authors.affiliation: Department of Preclinical Sciences, University of Milan Medical School, Via GB Grassi 74, Milan, Italy. jeanette.maier@unimi.it
authors.forename: Massimo
authors.initials: M
authors.lastname: Mariotti
authors.forename: Sara
authors.initials: S
authors.lastname: Castiglioni
authors.forename: Jose M
authors.initials: JM
authors.lastname: Garcia-Manteiga
authors.forename: Laura
authors.initials: L
authors.lastname: Beguinot
authors.forename: Jeanette A M
authors.initials: JA
authors.lastname: Maier