NEUROPEPTIDES STIMULATE TYROSINE PHOSPHORYLATION AND TYROSINE KINASE-ACTIVITY IN SMALL-CELL LUNG-CANCER CELL-LINES

Stimulation of small cell lung cancer (SCLC) cells with neuropeptides bombesin, bradykinin, gastrin, and neurotensin resulted in increased t yrosine kinase activity and tyrosine phosphorylation of a number of po lypeptides including a p120 kDa polypeptide identified by immunoblotti ng as focal adhesion kinase (p125(FAK)). The neuropeptides stimulated a rapid, concentration-dependent phosphorylation of p125(FAK) (EC(50) of 1 nM, 5 nM, and 2 nM for bombesin, bradykinin, and gastrin, respect ively), 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 b asal and neuropeptide stimulated SCLC cell growth. These results ident ify a novel neuropeptide-stimulated growth signaling event in SCLC cel ls.