EphrinA1 inactivates integrin-mediated vascular smooth muscle cell spreading via the Rac/PAK pathway

摘要: Interactions between the Eph receptor tyrosine kinase and ephrin ligands transduce short-range signals regulating axon pathfinding, development of cardiovascular system, as well migration spreading neuronal non-neuronal cells. Some these effects are believed to be mediated by alterations in actin dynamics. The members small Rho GTPase family elicit various on structures probably involved receptor-induced modulation. EphrinA1 is proposed contribute angiogenesis it strongly expressed at sites neovascularization. Moreover, angiogenic factors induce expression ephrinA1 endothelial In this study, using rat vascular smooth muscle cells (VSMCs), we investigated contribution GTPases ephrinA1-induced integrin inactivation. did not significantly affect early adhesion VSMCs purified laminin or fibronectin, but impaired cell spreading. inhibitor Y-27632 partly reversed effect, suggesting involvement model. However, inhibition RhoA synthesis with short interfering (si)RNA had a modest that plays limited role ephrinA1-mediated VSMCs. morphological correlated Rac1 p21-activated 1 (PAK1) activity, were antagonized constitutively active Rac mutant. repression siRNA amplifies Finally, sphingosine-1-phosphate (S1P), lipid mediator known inhibit activation effect. conclusion, our results emphasize Rac/PAK pathway way, ephrinA1, alone synergy S1P, can participate blood vessel destabilization, prerequisite for angiogenesis.