Neurotensin causes tyrosine phosphorylation of focal adhesion kinase in lung cancer cells.
The effects of neurotensin on focal adhesion kinase were investigated using lung cancer cells. Neurotensin bound with high affinity to large cell carcinoma cell line NCI-H1299 as did neurotensin-(8-13), but not neurotensin-(1-7) or levocabastine. Addition of 100 nM neurotensin to NCI-H1299 cells caused transient tyrosine phosphorylation of focal adhesion kinase which was maximal after 1-2.5 min. Also, neurotensin-(8-13), but not neurotensin-(1-8) or levocabastine, caused tyrosine phosphorylation of focal adhesion kinase after addition to NCI-H1299 cells. Focal adhesion kinase tyrosine phosphorylation caused by neurotensin was inhibited by the nonpeptide neurotensin receptor antagonist (2-(1-(7-chloroquinolin-4-yl)-5-(2,6-dimethoxyphenyl)-1H-pyrazole-3-carbonyl)amino)-adamantane-2-carboxylic acid) (SR48692). SR48692 inhibited the clonal growth of NCI-H1299 cells, whereas neurotensin-stimulated proliferation and levocabastine had no effect. These results indicate that lung cancer cells have functional neurotensin receptors which regulate focal adhesion kinase tyrosine phosphorylation. It remains to be determined if neurotensin receptors and focal adhesion kinase plays a role in lung cancer cellular adhesion and migration.
Leyton
Julius
J
Cell and Cancer Biology Department, Medicine Branch, National Cancer Institute, National Institutes of Health, Bldg. KWC, Rm. 300, 9610 Medical Center Drive, Rockville, MD 20850, USA.
Garcia-Marin
Luis
L
Jensen
Robert T
RT
Moody
Terry W
TW
D001667:Binding, Competitive / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D015638:Cytochalasin D / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism* / Q000473:pathology; D009496:Neurotensin / Q000378:metabolism / Q000494:pharmacology*; D019384:Nucleic Acid Synthesis Inhibitors / Q000494:pharmacology; D010446:Peptide Fragments / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects; D010880:Piperidines / Q000494:pharmacology; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D011720:Pyrazoles / Q000378:metabolism / Q000494:pharmacology; D011804:Quinolines / Q000378:metabolism / Q000494:pharmacology; D018028:Receptors, Neurotensin / Q000037:antagonists & inhibitors; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism; D014443:Tyrosine / Q000378:metabolism
D019384:Nucleic Acid Synthesis Inhibitors; D010446:Peptide Fragments; D010880:Piperidines; D011720:Pyrazoles; D011804:Quinolines; D018028:Receptors, Neurotensin; C409806:neurotensin (9-13); C079087:SR 48692; D015638:Cytochalasin D; D009496:Neurotensin; D014443:Tyrosine; D011505:Protein-Tyrosine Kinases; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; C496050:PTK2 protein, human; C047340:levocabastine