PROTEOLYTIC ACTIVATION OF A SINGLE-CHAIN PRECURSOR OF HEPATOCYTE GROWTH-FACTOR BY EXTRACELLULAR SERINE-PROTEASE

被引:53
作者
MIZUNO, K [1 ]
TAKEHARA, T [1 ]
NAKAMURA, T [1 ]
机构
[1] KYUSHU UNIV,FAC SCI,DEPT BIOL,FUKUOKA 812,JAPAN
关键词
D O I
10.1016/0006-291X(92)90264-L
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Hepatocyte growth factor (HGF) is biosynthesized as a single-chain precursor (pro-HGF) and is proteolytically processed to a two-chain mature form. When MRC-5 fibroblasts were pulse-radiolabeled under serum-free conditions, pro-HGF was the predominant molecular form of HGF in the culture medium. CHO cells transfected with an expression plasmid containing a full-size human HGF cDNA produced pro-HGF when these cells were cultured in serum-free medium. These findings suggest that HGF is secreted as a pro-form, which is then converted to a two-chain form by extracellular protease. Single-chain HGF exhibited mitogenic activity on cultured hepatocytes, with a potency similar to that of mature HGF, but this activity was remarkably inhibited by leupeptin. We postulate that inactive pro-HGF is converted to an active two-chain form by a leupeptin-sensitive serine-protease expressed by hepatocytes. Neither plasminogen activators nor plasmin showed any processing activity of pro-HGF in vitro. © 1992.
引用
收藏
页码:1631 / 1638
页数:8
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