PROTEOLYTIC ACTIVATION OF A SINGLE-CHAIN PRECURSOR OF HEPATOCYTE GROWTH-FACTOR BY EXTRACELLULAR SERINE-PROTEASE
PROTEOLYTIC ACTIVATION OF A SINGLE-CHAIN PRECURSOR OF HEPATOCYTE GROWTH-FACTOR BY EXTRACELLULAR SERINE-PROTEASE
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DOI：
10.1016/0006-291x(92)90264-l
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发表时间：
1992-12-30
影响因子：
3.1
通讯作者：
NAKAMURA, T
中科院分区：
文献类型：
--
作者：
MIZUNO, K;TAKEHARA, T;NAKAMURA, T
肝细胞生长因子（HGF）是生物合成的单链前体（pro-HGF），并通过蛋白水解加工成双链成熟形式。当MRC-5成纤维细胞在无血清条件下脉冲放射性标记时，促HGF是培养基中HGF的主要分子形式。用含有全长人HGF cDNA的表达质粒转染的CHO细胞在无血清培养基中培养时产生pro-HGF。这些发现表明HGF以前体形式分泌，然后通过细胞外蛋白酶转化为双链形式。单链HGF对培养的肝细胞具有促有丝分裂活性，其效力与成熟HGF相似，但亮抑酶肽显著抑制该活性。我们推测，无活性的促肝细胞生长因子原通过肝细胞表达的亮抑酶肽敏感的丝氨酸蛋白酶转化为活性的双链形式。纤溶酶原激活剂和纤溶酶在体外均未显示出对pro-HGF的加工活性。
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-HGFin vitro.