Endothelial migration, pivotal step of angiogenesis, is tightly tuned by tyrosine phosphorylation of different substrates, which results from the coordinated action of tyrosine kinases and phosphatases. Here we report that the tyrosine phosphatase HD-PTP has a role in modulating endothelial motility. Indeed, we found that endothelial cells downregulating HD-PTP after transfection with siRNA acquire a scattered and spindle-shaped phenotype and migrate more than controls. We also show that HD-PTP binds Focal Adhesion Kinase (FAK), a crucial regulator of cell migration. This interaction is strongly inhibited by treatment with basic Fibroblast Growth Factor, an angiogenic factor which stimulates endothelial cell migration. In cells downregulating HD-PTP, FAK is hyperphosphorylated on tyrosine residues and localizes in the focal adhesions, at the leading edge of the cell. We suggest that HD-PTP contributes to the regulation of endothelial motility by modulating the tyrosine phosphorylation of FAK.
|Titolo:||The tyrosine phosphatase HD-PTP : A novel player in endothelial migration|
|Parole Chiave:||HD-PTP ; FAK ; endothelium ; cell migration|
|Settore Scientifico Disciplinare:||Settore MED/04 - Patologia Generale|
|Data di pubblicazione:||2007|
|Digital Object Identifier (DOI):||10.1016/j.bbrc.2007.10.022|
|Appare nelle tipologie:||01 - Articolo su periodico|