Urokinase/urokinase receptor and vitronectin/alpha(v)beta(3) integrin induce chemotaxis and cytoskeleton reorganization through different signaling pathways

Vitronectin (VN) and pro-urokinase (pro-uPA) stimulated migration of rat sm ooth muscle cells in a dose-dependent and additive way, and induced motile- type changes in cell morphology together with a complete reorganization of the actin filaments and of the microtubules, All these effects were inhibit ed by pertussis toxin, or by antibodies directed against the urokinase rece ptor (uPAR) or against the VN receptor alpha (v)beta (3) suggesting that an association between the two receptors is required to mediate both signals. Investigation of the signaling pathways showed that increasing the intrace llular cAMP resulted in a selective inhibition of VN-induced cell migration . On the other hand, PD 98059, an inhibitor of MEK, differentially inhibite d the pro-uPA but not the VN-induced cell migration. Phosphorylation and nu clear translocation of Erk by pro-uPA was directly observed. We conclude th at the signaling pathways of pro-uPA and VN must be at least in part differ ent.