Urokinase-type plasminogen activator: protease and mitogen

The proliferation of vascular smooth muscle cells (SMCs) is a key step in atherosclerosis and is accompanied by upregulation of the serine protease urokinase-type plasminogen activator (UPA). The proteolytic activity of UPA is important for tissue remodelling, but UPA also appears to function in signal transduction - for example, by binding to the receptor CD87. Since growth factors expressed during atherosclerosis promote UPA production, Joachim Kienast and co-workers have investigated whether UPA has a role in growth factor signalling (see p. 1961). The authors show that antibodies against endogenous UPA block stimulation of DNA synthesis and SMC proliferation by PDGF and basic FGF(bFGF). Interestingly, the effects of PDGF/bFGF do not depend on UPA-CD87 interaction but seem to require casein kinase 2 (CK2). The authors thus propose that stimulation of SMC proliferation by PDGF/bFGF involves a UPA/CK2-dependent, CD87-independent pathway. Given that the C-terminal(catalytic) domain of UPA is required both for the mitogenic effects and for any undesirable proteolysis, it might represent a good target for anti-atherogenesis therapies.