Plasmin cleaves the juxtamembrane domain and releases truncated species of the urokinase receptor (CD87) from human bronchial epithelial cells

The three-domain (D1D2D3) urokinase receptor (CD87) is highly susceptible to cleavage within the D1-D2 linker sequence, but also within the juxtamembrane region by yet poorly characterized proteinases, allowing the release of D1 and D2D3 species in various (patho)physiological body fluids. Using immunoblot analysis and ELISA applied to a recombinant soluble CD87 and to CD87-expressing epithelial cells, we establish that exogenous or in situ generated plasmin proteolyzes CD87 in the D1-D2 linker and D3 carboxyterminal sequences, producing a major soluble D2D3 species. Mass spectrometry analysis of the fragmentation of CD87-related synthetic peptides, and aminoterminal sequencing of D2D3 reveal Arg(83), Arg(89), and Arg(281) as residues targeted by plasmin within human CD87. (C) 2004 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.