The hepatocyte growth factor and its receptor

Hepatocyte growth factor/scatter factor (HGF/SF) is secreted by cells of mesodermal origin and shows powerful mitogenic, motogenic and morphogenic activities on epithelial and endothelial cells. It is a heparin‐binding polypeptide with an α/β heterodimeric structure, showing structural homologies with enzymes of the blood clotting cascade. HGF binds with high affinity to the receptor encoded by the MET protooncogene (p190 MET ). The MET receptor is a heterodimer of two disulfide‐linked subunits (α and β); the α subunit is extracellular, while the β is transmembrane and endowed with tyrosine kinase activity. The HGF‐triggered signaling is mediated by different cytoplasmic effectors, including phosphatidylinositol 3‐kinase, phospholipase C‐γ, and Src‐related tyrosine kinases. p190 MET is expressed in several normal epithelial tissues (e.g., liver, gastrointestinal tract, kidney) and is often overexpressed in neoplastic cells. p190 MET expression has been reported also in central nervous system microglia, a monocyte‐derived cell population. We recently found that p190 MET is expressed in selected peripheral blood cell populations, such as macrophages. The amount of both mRNA and protein is barely detectable, while it is dramatically increased upon activation. These findings suggest that HGF may play a role in hemopoietic cell signaling, during activation and differentiation of blood cell lineages.