Activation of the protein-tyrosine kinase associated with the bombesin receptor complex in small cell lung carcinomas

Journal Article · Fri Apr 01 00:00:00 EST 1988 · Proceedings of the National Academy of Sciences of the United States of America; (USA)

DOI:https://doi.org/10.1073/pnas.85.7.2166· OSTI ID:6827907

Gaudino, G; Cirillo, D; Naldini, L; Rossino, P; Comoglio, P M ^[1]

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1. Univ. of Torino Medical School, Turin (Italy)

It has been hypothesized that bombesin-like peptides produced by small cell lung carcinomas may sustain deregulated proliferation through an autocrine mechanism. The authors have shown that the neuropeptide bombesin leads to the activation of a protein-tyrosine kinase that phosphorylates a 115-kDa protein (p115) associated with the bombesin receptor complex in mouse Swiss 3T3 fibroblasts. They now report that phosphotyrosine antibodies recognize a 115-kDa protein, phosphorylated on tyrosine, in four human small cell lung carcinoma cell lines producing bombesin but not in a nonproducer variant line. p115 from detergent-treated small cell lung carcinoma cells binds to bombesin-Sepharose and can be phosphorylated on tyrosine in the presence of radiolabeled ATP and Mn{sup 2+}. As for the p115 immunoprecipitated from mouse fibroblast, the small cell lung carcinoma p115 can be phosphorylated in an immunocomplex kinase assay. However, the latter does not require the presence of exogenous bombesin for activity. Binding data, obtained by using radiolabeled ligand, suggest receptor occupancy in the cell lines producing bombesin. These observations are consistent with the hypothesis that proliferation in some human small cell lung carcinoma lines is under autocrine control, regulated through activation of bombesin receptors.

• OSTI ID: 6827907
• Journal Information: Proceedings of the National Academy of Sciences of the United States of America; (USA), Vol. 85:7; ISSN 0027-8424
• Country of Publication: United States
• Language: English

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59 BASIC BIOLOGICAL SCIENCES
GROWTH FACTORS
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PHOSPHOTRANSFERASES
ENZYME INDUCTION
RECEPTORS
TUMOR CELLS
CELL PROLIFERATION
CARBON 14 COMPOUNDS
CARCINOMAS
FIBROBLASTS
IODINE 125
LIGANDS
METHIONINE
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ANIMAL CELLS
BETA DECAY RADIOISOTOPES
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CONNECTIVE TISSUE CELLS
DAYS LIVING RADIOISOTOPES
DISEASES
DRUGS
ELECTRON CAPTURE RADIOISOTOPES
ENZYMES
EVEN-ODD NUCLEI
GENE REGULATION
HYDROXY ACIDS
INTERMEDIATE MASS NUCLEI
IODINE ISOTOPES
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LABELLED COMPOUNDS
LIGHT NUCLEI
LIPOTROPIC FACTORS
MEMBRANE PROTEINS
MITOGENS
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NUCLEI
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ORGANIC ACIDS
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ORGANIC SULFUR COMPOUNDS
PHOSPHORUS-GROUP TRANSFERASES
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SULFUR ISOTOPES
TRANSFERASES
550301* - Cytology- Tracer Techniques