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HD-PTP inhibits endothelial migration through its interaction with Src
- Source :
-
International Journal of Biochemistry & Cell Biology . Mar2009, Vol. 41 Issue 3, p687-693. 7p. - Publication Year :
- 2009
-
Abstract
- 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. [Copyright &y& Elsevier]
Details
- Language :
- English
- ISSN :
- 13572725
- Volume :
- 41
- Issue :
- 3
- Database :
- Academic Search Index
- Journal :
- International Journal of Biochemistry & Cell Biology
- Publication Type :
- Academic Journal
- Accession number :
- 36105871
- Full Text :
- https://doi.org/10.1016/j.biocel.2008.08.005