Oncogenic forms of the neu/HER2 tyrosine kinase are permanently coupled to phospholipase C gamma.

摘要: The neu/HER2 proto-oncogene encodes a transmembrane tyrosine kinase homologous to receptors for polypeptide growth factors. oncogenic potential the presumed receptor is released through multiple genetic mechanisms including specific point mutation, truncation at extracellular domain and overexpression of protooncogene. Here we show that all these modes activation result in constitutively phosphorylated neu protein an increase phosphorylation phosphatidylinositol-specific phospholipase (PLC gamma). examined transforming proteins, unlike normal gene product, also co-immunoprecipitated with PLC gamma molecules. A kinase-defective mutant failed mediate both association gamma, suggesting direct interaction gamma. This possibility was by employing chimeric composed ligand-binding epidermal factor cytoplasmic portion. mediated rapid ligand-dependent modification on residues. It physically associated, manner, phosphoinositidase. Based presented results suggest mechanism cellular transformation involves