title: Shedding and cleavage of the urokinase receptor (uPAR): identification and characterisation of uPAR fragments in vitro and in vivo.
abstract: Applying a novel, highly specific and sensitive immunoabsorption/Western blotting technique we have identified in vitro in conditioned cell culture medium and in vivo in human urine different soluble forms of the urokinase-type plasminogen activator receptor (uPAR/CD87). These include the uPAR fragment D2D3 and the never before identified domain 1 (D1) fragment. These forms correspond to fragments previously characterised as biologically active as inducers of chemotaxis and cell adhesion. We find that stimulation of U937 cells is associated with increased uPAR expression, cleavage of surface uPAR, and release of soluble fragments to the culture medium suggesting that monocytes are a source of the circulating and urinary soluble uPAR fragments found in vivo. Our study demonstrates that potentially biologically active uPAR fragments are produced in the human body, indicating a possible function in the regulation of not only proteolysis but also signal transduction related processes.
authors.affiliation: Department of Molecular Pathology and Medicine, Molecular Genetics Unit, DIBIT, San Raffaele Scientific Institute, Via Olgettina 58, 20132, Milan, Italy. sidenius.nicolai@hsr.it
authors.forename: N
authors.initials: N
authors.lastname: Sidenius
authors.forename: C F
authors.initials: CF
authors.lastname: Sier
authors.forename: F
authors.initials: F
authors.lastname: Blasi
mesh_terms: D006801:Humans; D010446:Peptide Fragments / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000737:chemistry / Q000378:metabolism*; D055293:Receptors, Urokinase Plasminogen Activator; D015398:Signal Transduction; D014568:Urokinase-Type Plasminogen Activator / Q000737:chemistry / Q000378:metabolism
chemical_list: C524898:PLAUR protein, human; D010446:Peptide Fragments; D011956:Receptors, Cell Surface; D055293:Receptors, Urokinase Plasminogen Activator; D014568:Urokinase-Type Plasminogen Activator