Shedding and cleavage of the urokinase receptor (uPAR): identification andcharacterisation of uPAR fragments in vitro and in vivo

Applying a novel, highly specific and sensitive immunoabsorption/Western bl otting technique we have identified in vitro in conditioned cell culture me dium and in vivo in human urine different soluble forms of the urokinase-ty pe plasminogen activator receptor (uPAR/CD87). These include the uPAR fragm ent D2D3 and the never before identified domain 1 (D1) fragment. These form s correspond to fragments previously characterised as biologically active a s inducers of chemotaxis and cell adhesion. We find that stimulation of U93 7 cells is associated with increased uPAR expression, cleavage of surface u PAR, and release of soluble fragments to the culture medium suggesting that monocytes are a source of the circulating and urinary soluble uPAR fragmen ts found in vivo. Our study demonstrates that potentially biologically acti ve uPAR fragments are produced in the human body, indicating a possible fun ction in the regulation of not only proteolysis but also signal transductio n related processes. (C) 2000 Federation of European Biochemical Societies. Published by Elsevier Science B.V. All rights reserved.