Naka D, Ishii T, Yoshiyama Y, Miyazawa K, Hara H, Hishida T, Kidamura N
Biosciences Laboratory, Mitsubishi Kasei Corporation, Yokohama, Japan.
J Biol Chem. 1992 Oct 5;267(28):20114-9.
Hepatocyte growth factor (HGF) is a heterodimeric protein consisting of a heavy chain and a light chain held by a disulfide bond. These chains are produced by endoproteolytic processing from a single chain precursor. In this study, we examined whether the processing is a prerequisite for the mitogenic activity of HGF on hepatocytes in primary culture. Single chain HGF was proteolytically converted to the heterodimeric form during incubation with hepatocytes and was as mitogenic as the heterodimeric form. When the conversion was inhibited by serine-protease inhibitors, the mitogenic activity of single chain HGF was markedly reduced. Furthermore, a mutant resistant to the proteolytic processing, which was prepared by in vitro mutagenesis, completely lost the mitogenic activity. From these results, we concluded that the single chain form of HGF is endoproteolytically processed by a serine-protease and that this processing is a prerequisite for the mitogenic activity of HGF.
肝细胞生长因子（HGF）是一种异二聚体蛋白，由通过二硫键连接的重链和轻链组成。这些链是由单链前体经内切蛋白水解加工产生的。在本研究中，我们检测了这种加工是否是HGF对原代培养肝细胞促有丝分裂活性的前提条件。单链HGF在与肝细胞孵育过程中被蛋白水解转化为异二聚体形式，并且与异二聚体形式一样具有促有丝分裂作用。当这种转化被丝氨酸蛋白酶抑制剂抑制时，单链HGF的促有丝分裂活性显著降低。此外，通过体外诱变制备的对蛋白水解加工有抗性的突变体完全丧失了促有丝分裂活性。从这些结果中，我们得出结论，HGF的单链形式经丝氨酸蛋白酶进行内切蛋白水解加工，并且这种加工是HGF促有丝分裂活性的前提条件。
