Hepatocyte growth factor induces activation of Nck and phospholipase C-gamma in lung carcinoma cells.
Hepatocyte growth factor (HGF), a mesenchyme derived growth factor, promotes cell growth, cell motility, and morphogenesis in a variety of epithelial cells. The diverse responses are transduced across the cell membrane by the met/HGF receptor, a product of c-met protooncogene. The met/HGF receptor recruits a variety of second messenger molecules which relay the diverse intracellular responses of HGF. In this study, we show that HGF autophosphorylates and activates met/HGF receptor. The activated met/HGF receptor then physically associates with and activates phospholipase C-gamma (PLC-gamma). Furthermore, upon ligand stimulation, tyrosine-autophosphorylated met/HGF receptor also activates Nck oncogene product. Taken together, our results suggest that the receptor activation leads to formation of a complex in which PLC-gamma and Nck oncogene product co-exist with the activated met/HGF receptor, and that the Nck oncogene product is an important component of HGF signaling in Calu-1 and A549 cells.
Kochhar
K S
KS
Department of Pathology, Northwestern University Medical School, Chicago, IL 60611, USA.
Iyer
A P
AP
D048868:Adaptor Proteins, Signal Transducing; D004789:Enzyme Activation; D017228:Hepatocyte Growth Factor / Q000494:pharmacology*; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism*; D015513:Oncogene Proteins / Q000187:drug effects* / Q000378:metabolism; D010766:Phosphorylation; D019859:Proto-Oncogene Proteins c-met; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism; D014407:Tumor Cells, Cultured; D010738:Type C Phospholipases / Q000187:drug effects* / Q000378:metabolism
D048868:Adaptor Proteins, Signal Transducing; C078332:Nck protein; D015513:Oncogene Proteins; D017228:Hepatocyte Growth Factor; D019859:Proto-Oncogene Proteins c-met; D020794:Receptor Protein-Tyrosine Kinases; D010738:Type C Phospholipases