Tyrosine phosphatase εM stimulates migration and survival of porcine aortic endothelial cells by activating c-Src

Abstract

The cell growth, survival, and migration of vascular endothelial cells (ECs) are positively regulated by several protein tyrosine kinase receptors. Therefore, protein tyrosine phosphatases (PTPs) must also be important for these processes. The present study found that transmembranal PTPεM, but not cytoplasmic PTPεC, is expressed in porcine ECs and in rat smooth muscle cells, both of which were prepared from the aorta. The overexpression of wild-type PTPεM promoted cell survival and migration in porcine aortic ECs even in medium without and with 1% serum, respectively. A catalytically inactive, substrate-trapping mutant of PTPεM, respectively, did not affect and conversely suppressed cell survival and migration. Interestingly, the forced expression of wild-type PTPεC reduced cell viability in contrast to PTPεM in ECs lacking endogenous PTPεC, indicating the biological significance of selective expression of PTPε isoforms in the vasculature. PTPεM activated c-Src kinase probably by directly dephosphorylating phospho-Tyr527, a negative regulatory site of c-Src. The increases in cell survival and migration induced by overexpressed PTPεM were suppressed by the c-Src inhibitor SU6656. Considering the behaviors of vascular ECs in the pathogenesis of atherosclerosis, these data suggest that PTPεM negatively regulates the development of this disease by activating c-Src.