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 Arg83, Arg89, and Arg281 as residues targeted by plasmin within human CD87.
Beaufort
Nathalie
N
Unité de Défense Innée et Inflammation/Inserm E336, Département de Médecine Moléculaire, Institut Pasteur, 25-28 rue du Docteur Roux, F-75724 Paris Cedex 15, France. beaufort@pasteur.fr
Leduc
Dominique
D
Rousselle
Jean-Claude
JC
Namane
Abdelkader
A
Chignard
Michel
M
Pidard
Dominique
D
D001980:Bronchi / Q000166:cytology / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D004847:Epithelial Cells / Q000378:metabolism; D005341:Fibrinolysin / Q000378:metabolism*; D006801:Humans; D011956:Receptors, Cell Surface / Q000378:metabolism*; D055293:Receptors, Urokinase Plasminogen Activator; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
C524898:PLAUR protein, human; D011956:Receptors, Cell Surface; D055293:Receptors, Urokinase Plasminogen Activator; D005341:Fibrinolysin