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

FEBS Letters

Sier, Cornelis F.M¹  Sidenius, Nicolai¹  Blasi, Francesco¹ 

[1] Department of Molecular Pathology and Medicine, Molecular Genetics Unit, DIBIT, San Raffaele Scientific Institute, Via Olgettina 58, 20132 Milan, Italy

关键词: Urokinase-type plasminogen activator receptor;    Fragment;    Cleavage;    Shedding;    Plasma;    Urine;    ELISA;    enzyme-linked immunosorbent assay;    GPI;    glycosylphosphatidylinositol;    PMA;    12-O-tetradecanoylphorbol-13-acetate;    (pro)uPA;    (pro-)urokinase-type plasminogen activator;    (s)uPAR;    (soluble) uPA receptor;   

DOI  :  10.1016/S0014-5793(00)01624-0

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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.

【 授权许可】

Unknown