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 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.
Tallett
A
A
Respiratory Medicine Unit (RIE), Rayne Laboratory, University of Edinburgh Medical School, UK.
Chilvers
E R
ER
MacKinnon
A C
AC
Haslett
C
C
Sethi
T
T
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
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