title: Evidence showing that the two-chain form of vitronectin is produced in the liver by a selective furin cleavage.
abstract: The adhesive protein vitronectin (75 kDa) occurs in human blood fluid in a one-chain (Vn75) or a two-chain form (Vn65-10), and is produced by a specific cleavage (at Arg379-Ala380), by a proteinase not identified hitherto. These two forms were shown to be functionally different and therefore, this cleavage may have a regulatory significance in vivo. Here, we report the use of a tailored one-chain recombinant Vn, a specific protein kinase A phosphorylation at Ser378, and sequence analysis to show: (1) that none of the proteinases originating from blood, previously thought to be the endogenous proteinase (plasmin, thrombin, tPA, and uPA), is indeed the in vivo convertase; and (2) that furin, a serine endoproteinase residing in the secretory pathway of hepatocytes, where Vn is synthesized, specifically cleaves Vn at the endogenous cleavage site. Consequently, we propose that the Vn75 to Vn65-10 conversion takes place in the liver (not in blood) and is carried out by furin.
authors.affiliation: Department of Biological Regulation, The Weizmann Institute of Science, Rehovot, Israel.
authors.forename: D
authors.initials: D
authors.lastname: Seger
authors.forename: S
authors.initials: S
authors.lastname: Shaltiel
mesh_terms: D000409:Alanine / Q000378:metabolism; D001120:Arginine / Q000378:metabolism; D005341:Fibrinolysin / Q000378:metabolism; D045683:Furin; D015870:Gene Expression; D006801:Humans; D008099:Liver / Q000378:metabolism*; D020033:Protein Isoforms / Q000096:biosynthesis / Q000235:genetics / Q000302:isolation & purification; D013381:Subtilisins / Q000378:metabolism*; D010959:Tissue Plasminogen Activator / Q000378:metabolism; D014568:Urokinase-Type Plasminogen Activator / Q000378:metabolism; D019096:Vitronectin / Q000096:biosynthesis* / Q000235:genetics / Q000302:isolation & purification
chemical_list: D020033:Protein Isoforms; D019096:Vitronectin; D001120:Arginine; D013381:Subtilisins; D010959:Tissue Plasminogen Activator; D005341:Fibrinolysin; D014568:Urokinase-Type Plasminogen Activator; D045683:Furin; D000409:Alanine