Activation of the protein-tyrosine kinase associated with the bombesin receptor complex in small cell lung carcinomas.
It has been hypothesized that bombesin-like peptides produced by small cell lung carcinomas may sustain deregulated proliferation through an autocrine mechanism. We have shown that the neuropeptide bombesin leads to the activation of a protein-tyrosine kinase that phosphorylates a 115-kDa protein (p115) associated with the bombesin receptor complex in mouse Swiss 3T3 fibroblasts. We now report that phosphotyrosine antibodies recognize a 115-kDa protein, phosphorylated on tyrosine, in four human small cell lung carcinoma cell lines producing bombesin but not in a nonproducer "variant" line. p115 from detergent-treated small cell lung carcinoma cells binds to bombesin-Sepharose and can be phosphorylated on tyrosine in the presence of radiolabeled ATP and Mn2+. As for the p115 immunoprecipitated from mouse fibroblast, the small cell lung carcinoma p115 can be phosphorylated in an immunocomplex kinase assay. However, the latter does not require the presence of exogenous bombesin for activity. Binding data, obtained by using radiolabeled ligand, suggest receptor occupancy in the cell lines producing bombesin. These observations are consistent with the hypothesis that proliferation in some human small cell lung carcinoma lines is under autocrine control, regulated through activation of bombesin receptors.
D000818:Animals; D001839:Bombesin / Q000378:metabolism / Q000494:pharmacology*; D018288:Carcinoma, Small Cell / Q000032:analysis* / Q000378:metabolism; D002460:Cell Line; D004789:Enzyme Activation; D005347:Fibroblasts / Q000032:analysis; D006801:Humans; D008175:Lung Neoplasms / Q000032:analysis* / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D009363:Neoplasm Proteins / Q000378:metabolism*; D010750:Phosphoproteins / Q000378:metabolism*; D010766:Phosphorylation; D019000:Phosphotyrosine; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D018004:Receptors, Bombesin; D017981:Receptors, Neurotransmitter / Q000187:drug effects*; D014407:Tumor Cells, Cultured / Q000032:analysis; D014443:Tyrosine / Q000031:analogs & derivatives / Q000276:immunology
D008565:Membrane Proteins; D009363:Neoplasm Proteins; D010750:Phosphoproteins; D018004:Receptors, Bombesin; D017981:Receptors, Neurotransmitter; D019000:Phosphotyrosine; D014443:Tyrosine; D011505:Protein-Tyrosine Kinases; D001839:Bombesin