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Molecular cloning and expression of human hepatocyte growth factor

Abstract

HEPATOCYTE growth factor (HGF) is the most potent mitogen for mature parenchyma! hepatocytes in primary culture, and seems to be a hepatotrophic factor that acts as a trigger for liver regeneration after partial hepatectomy and liver injury. The partial purification and characterization of HGF have been reported1–4. We have demonstrated that pure HGF from rat platelets is a new growth factor5, 6 effective at concentrations as low as 1 ng mP−1.The effects of HGF and epidermal growth factor (EGF) are additive. The activity of HGF is not species-specific, although it does not stimulate growth in Swiss 3T3 fibroblasts5. HGF has a relative molecular mass (Mr) of 82,000 and is a heterodimer composed of a large a-subunit of Mr 69,000 and a small β -subunit of Mr34,000 (ref. 6). Here we report the amino-acid sequence of human HGF determined by complementary DNA cloning and the expression of biologically active human HGF from COS-1 cells transfected with cloned cDNA. The nucleotide sequence of the human HGF cDNA reveals that both α- andβ-chains are contained in a single open reading frame coding for a pre-pro precursor protein of 728 amino acids.

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Nakamura, T., Nishizawa, T., Hagiya, M. et al. Molecular cloning and expression of human hepatocyte growth factor. Nature 342, 440–443 (1989). https://doi.org/10.1038/342440a0

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