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Dimerization controls the lipid raft partitioning of uPAR/CD87 and regulates its biological functions
Author(s) -
Cunningham Orla,
Andolfo Annapaola,
Santovito Maria Lisa,
Iuzzolino Lucia,
Blasi Francesco,
Sidenius Nicolai
Publication year - 2003
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1093/emboj/cdg588
Subject(s) - functional genomics , biology , molecular genetics , genomics , computational biology , genetics , gene , genome
The urokinase‐type plasminogen activator receptor (uPAR/CD87) is a glycosylphosphatidylinositol‐anchored membrane protein with multiple functions in extracellular proteolysis, cell adhesion, cell migration and proliferation. We now report that cell surface uPAR dimerizes and that dimeric uPAR partitions preferentially to detergent‐resistant lipid rafts. Dimerization of uPAR did not require raft partitioning as the lowering of membrane cholesterol failed to reduce dimerization and as a transmembrane uPAR chimera, which does not partition to lipid rafts, also dimerized efficiently. While uPA bound to uPAR independently of its membrane localization and dimerization status, uPA‐induced uPAR cleavage was strongly accelerated in lipid rafts. In contrast to uPA, the binding of Vn occurred preferentially to raft‐associated dimeric uPAR and was completely blocked by cholesterol depletion.