HD-PTP inhibits endothelial migration through its interaction with Src.

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.

The tyrosine phosphatase HD-PTP is regulated by FGF-2 through proteasome degradation.

Angiogenesis is essential in development and wound healing and contributes to the pathogenesis of many diseases. The signalling pathways activated in angiogenesis are, in part ,known and the overall tyrosine phosphorylation of cellular proteins plays a relevant role. By RNA fingerprinting, we isolated a tyrosine phosphatase, HD-PTP, modulated in human endothelial cells exposed to human immunodeficiency virus type 1 Tat, a viral protein known to be angiogenic.

Effect of tyrosine kinase inhibitors on clathrin-coated pit recruitment and internalization of epidermal growth factor receptor.

Several inhibitors of epidermal growth factor receptor (EGFR) kinase and Src family kinases (SFK) were employed to study the role of these kinases in EGFR internalization through clathrin-coated pits. The EGFR kinase-specific compound PD158780 substantially diminished EGFR internalization. PP2, an inhibitor of SFK, had a moderate effect on EGFR internalization in several types of cells, including cells lacking SFK, indicating that the inhibition of endocytosis by PP2 is mediated by kinases other than SFK.

Integrin-induced epidermal growth factor (EGF) receptor activation requires c-Src and p130Cas and leads to phosphorylation of specific EGF receptor tyrosines.

Integrin-mediated cell adhesion cooperates with growth factor receptors in the control of cell proliferation, cell survival, and cell migration. One mechanism to explain these synergistic effects is the ability of integrins to induce phosphorylation of growth factor receptors, for instance the epidermal growth factor (EGF) receptor. Here we define some aspects of the molecular mechanisms regulating integrin-dependent EGF receptor phosphorylation.

Conformational analysis of the phosphorylated epidermal growth factor receptor.

Phosphorylation-induced conformational changes have been well documented with different receptor tyrosine kinases. However. the susceptible epitopes and the tyrosine residue(s) involved in particular structural alteration mostly remain to be determined.