Analysis of deleted variant of hepatocyte growth factor by alanine scanning mutagenesis: identification of residues essential for its biological function and generation of mutants with enhanced mitogenic activity on rat hepatocytes.

To understand the structure-function relationship of hepatocyte growth factor (HGF) in more detail, we analyzed one of the other forms of HGF, deleted variant of HGF (dHGF), by alanine scanning mutagenesis. We show here that there are at least four sites important for dHGF to stimulate DNA synthesis in cultured adult rat hepatocytes, and that the residues of HGF essential for exerting its biological activity are not identical to those of dHGF. In addition, two mutants showed a decrease (approximately three-fold) in EC50 compared with wild-type dHGF in an assay of mitogenic activity on rat hepatocytes.