Evidence showing that the two‐chain form of vitronectin is produced in the liver by a selective furin cleavage

FEBS Letters

Shaltiel, Shmuel¹  Seger, Dalia¹ 

[1] Department of Biological Regulation, The Weizmann Institute of Science, IL-76100 Rehovot, Israel

关键词: Vitronectin;    Furin;    Adhesive protein;    Fibrinolysis;    Heparin;    Extracellular matrix;   

DOI  :  10.1016/S0014-5793(00)01917-7

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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.

【 授权许可】

Unknown