HEPATOCYTE GROWTH-FACTOR INDUCES ACTIVATION OF NCK AND PHOSPHOLIPASE C-GAMMA IN LUNG-CARCINOMA CELLS

Hepatocyte growth factor (HGF), a mesenchyme derived growth factor, pr omotes cell growth, cell motility, and morphogenesis in a variety of e pithelial cells. The diverse responses are transduced across the cell membrane by the met/HGF receptor, a product of c-met protooncogene. Th e met/HGF receptor recruits a variety of second messenger molecules wh ich relay the diverse intracellular responses of HGF. In this study, w e show that HGF autophosphorylates and activates met/HGF receptor. The activated met/HGF receptor then physically associates with and activa tes phospholipase C-gamma (PLC-gamma). Furthermore, upon ligand stimul ation, tyrosine-autophosphorylated met/HGF receptor also activates Nck oncogene product. Taken together, our results suggest that the recept or activation leads to formation of a complex in which PLC-gamma and N ck oncogene product co-exist with the activated met/HGF receptor, and that the Nck oncogene product is an important component of HGF signali ng in Calu-1 and A549 cells.