Neuropeptides stimulate tyrosine phosphorylation and tyrosine kinase activity in small cell lung cancer cell lines

• Published in: Peptides (New York, N.Y. : 1980) N.Y. : 1980), 1996, Vol.17 (4), p.665-673
• Main Authors: Tallett, A., Chilvers, E.R., MacKinnon, A.C., Haslett, C., Sethi, T.
• Format: Article
• Language: English
• Subjects: Bombesin - pharmacology; Bradykinin - pharmacology; Carcinoma, Small Cell; Cell Adhesion Molecules - metabolism; Cell Line; Focal adhesion kinase; Focal Adhesion Kinase 1; Focal Adhesion Protein-Tyrosine Kinases; Gastrins - pharmacology; Growth; Humans; Kinetics; Lung Neoplasms; Neuropeptide; Neuropeptides - pharmacology; Neurotensin - pharmacology; Phosphoproteins - analysis; Phosphoproteins - metabolism; Phosphorylation; Phosphotyrosine - metabolism; Protein-Tyrosine Kinases - metabolism; Signal transduction; Small cell lung cancer; Tumor Cells, Cultured; Tyrosine; Tyrosine kinase activity; Tyrosine phosphorylation
• ISSN: 0196-9781; 1873-5169
• DOI: 10.1016/0196-9781(96)00055-1

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 (p125 FAK). The neuropeptides stimulated a rapid, concentration-dependent phosphorylation of p125 FAK (EC 50 of 1 n M, 5 n M, and 2 n M 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.