title: Neuropeptides stimulate tyrosine phosphorylation and tyrosine kinase activity in small cell lung cancer cell lines.
abstract: Stimulation of small cell lung cancer (SCLC) cells with neuropeptides bombesin, bradykinin, gastrin, and neurotensin resulted in increased tyrosine kinase activity and tyrosine phosphorylation of a number of polypeptides including a p120 kDa polypeptide identified by immunoblotting as focal adhesion kinase (p125FAK). The neuropeptides stimulated a rapid, concentration-dependent phosphorylation of p125FAK (EC50 of 1 nM, 5 nM, and 2 nM for bombesin, bradykinin, and gastrin, respectively), which was receptor mediated and inhibited by both specific and broad-spectrum neuropeptide receptor antagonists. Specific inhibition of protein tyrosine kinase activity by tyrphostin-25 inhibited both basal and neuropeptide-stimulated SCLC cell growth. These results identify a novel neuropeptide-stimulated growth signaling event in SCLC cells.
authors.affiliation: Respiratory Medicine Unit (RIE), Rayne Laboratory, University of Edinburgh Medical School, UK.
authors.forename: A
authors.initials: A
authors.lastname: Tallett
authors.forename: E R
authors.initials: ER
authors.lastname: Chilvers
authors.forename: A C
authors.initials: AC
authors.lastname: MacKinnon
authors.forename: C
authors.initials: C
authors.lastname: Haslett
authors.forename: T
authors.initials: T
authors.lastname: Sethi
mesh_terms: D001839:Bombesin / Q000494:pharmacology; D001920:Bradykinin / Q000494:pharmacology; D018288:Carcinoma, Small Cell; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002460:Cell Line; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; D005755:Gastrins / Q000494:pharmacology; D006801:Humans; D007700:Kinetics; D008175:Lung Neoplasms; D009479:Neuropeptides / Q000494:pharmacology*; D009496:Neurotensin / Q000494:pharmacology; D010750:Phosphoproteins / Q000032:analysis / Q000378:metabolism; D010766:Phosphorylation; D019000:Phosphotyrosine / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D014443:Tyrosine
chemical_list: D015815:Cell Adhesion Molecules; D005755:Gastrins; D009479:Neuropeptides; D010750:Phosphoproteins; D019000:Phosphotyrosine; D009496:Neurotensin; D014443:Tyrosine; D011505:Protein-Tyrosine Kinases; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; C496050:PTK2 protein, human; D001839:Bombesin; D001920:Bradykinin