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 morph ogenic activities on epithelial and endothelial cells. It is a heparin -binding polypeptide with an alpha/beta heterodimeric structure, showi ng structural homologies with enzymes of the blood clotting cascade. H GF binds with high affinity to the receptor encoded by the MET proto-o ncogene (p190MET). The MET receptor is a heterodimer of two disulfide- linked subunits (alpha and beta); the alpha subunit is extracellular, while the beta is transmembrane and endowed with tyrosine kinase activ ity. The HGF-triggered signaling is mediated by different cytoplasmic effectors, including phosphatidylinositol 3-kinase, phospholipase C-ga mma, and Src-related tyrosine kinases. p190MET is expressed in several normal epithelial tissues (e.g., liver, gastrointestinal tract, kidne y) and is often overexpressed in neoplastic cellS. p190MET expression has been reported also in central nervous system microglia, a monocyte -derived cell population. We recently found that p190MET is expressed in selected peripheral blood cell populations, such as macrophages. Th e amount of both mRNA and protein is barely detectable, while it is dr amatically increased upon activation. These findings suggest that HGF may play a role in hemopoietic cell signaling, during activation and d ifferentiation of blood cell lineages.