The plasminogen activator (PA) system plays an important role in processes involving extracellular proteolysis, such as angiogenesis, wound healing, gametogenesis, inflammation and tumor metastasis.
Recent results show a new form of biological regulation by the PA system not involving proteolytic activity in which urokinase-type PA (uPA)-occupied uPA receptor acquires a high affinity for vitronectin, promoting cell adhesion or migration on vitronectin-containing extracellular matrix. Studying regulation of uPA and PA inhibitor-1 by growth factors, we found serine/threonine phosphorylation of the adaptor/docking protein ShcA. Tyrosine phosphorylation of ShcA and its role in signaling have been well documented, but its serine/threonine phosphorylation has been little studied. Our work has revealed a role for serine phosphorylation of ShcA in insulin induced signaling.