HD-PTP inhibits endothelial migration through its interaction with Src

M Mariotti, S Castiglioni, JM Garcia-Manteiga… - The international journal …, 2009 - Elsevier
M Mariotti, S Castiglioni, JM Garcia-Manteiga, L Beguinot, JAM Maier
The international journal of biochemistry & cell biology, 2009Elsevier
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 …
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.
Elsevier