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Evidence showing that the two‐chain form of vitronectin is produced in the liver by a selective furin cleavage
Author(s) -
Seger Dalia,
Shaltiel Shmuel
Publication year - 2000
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(00)01917-7
Subject(s) - furin , cleavage (geology) , proprotein convertase , biochemistry , phosphorylation , plasmin , vitronectin , serine , chemistry , proprotein convertases , in vivo , thrombin , microbiology and biotechnology , biology , enzyme , platelet , integrin , receptor , immunology , lipoprotein , paleontology , ldl receptor , cholesterol , fracture (geology)
The adhesive protein vitronectin (75 kDa) occurs in human blood fluid in a one‐chain (Vn 75 ) or a two‐chain form (Vn 65+10 ), and is produced by a specific cleavage (at Arg 379 –Ala 380 ), 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 Ser 378 , 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 Vn 75 to Vn 65+10 conversion takes place in the liver (not in blood) and is carried out by furin.