A tyrosine protein kinase activated by bombesin in normal fibroblasts and small cell carcinomas.
In Swiss 3T3 fibroblasts, antibodies which recognize a phosphotyrosine residue (P-Tyr antibodies) identify a 115-kDa cell surface protein (p115) that becomes phosphorylated on tyrosine as a response to bombesin stimulation of quiescent cells. The extent of phosphorylation is dose-dependent and correlates with the mitogenic effect induced by bombesin, measured by [3H]thymidine incorporation. Tyrosine phosphorylation of p115 is detectable minutes after addition of bombesin and precedes the activation of c-fos and c-myc gene transcription. Immunocomplexes of phosphorylated p115 with P-Tyr antibodies bind 125I-labeled [Tyr4]bombesin in a specific and saturable manner and display an associated tyrosine protein kinase activity enhanced by bombesin. P-Tyr antibodies also recognize a protein of 115 kDa, phosphorylated at tyrosine, in four human SCLC lines producing bombesin but not in a non-producer "variant" line. Phosphorylation of SCLC p115 does not require the addition of exogenous bombesin. As in the case of the p115 immunoprecipitated from mouse fibroblasts, the SCLC p115 is phosphorylated in an immunocomplex kinase assay. These observations are in agreement with the hypothesis of autocrine activation of bombesin receptors in human small cell lung carcinoma cells.
Gaudino
G
G
Department of Biomedical Sciences and Oncology, University of Torino Medical School, Italy.
Cilli
M
M
Gandino
L
L
Rossino
P
P
Mondino
A
A
Comoglio
P M
PM
D000818:Animals; D001839:Bombesin / Q000494:pharmacology*; D018288:Carcinoma, Small Cell; D002478:Cells, Cultured; D004789:Enzyme Activation; D005347:Fibroblasts / Q000201:enzymology; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D008175:Lung Neoplasms; D051379:Mice; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D011519:Proto-Oncogenes / Q000187:drug effects*; D012333:RNA, Messenger / Q000187:drug effects / Q000235:genetics; D018004:Receptors, Bombesin; D017981:Receptors, Neurotransmitter / Q000187:drug effects / Q000502:physiology; D014158:Transcription, Genetic / Q000187:drug effects; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000201:enzymology*
D012333:RNA, Messenger; D018004:Receptors, Bombesin; D017981:Receptors, Neurotransmitter; D011505:Protein-Tyrosine Kinases; D001839:Bombesin