Induction of Ornithine Decarboxylase Activity by Insulin and Growth Factors is Mediated by Amino Acids

• Published in: Proceedings of the National Academy of Sciences - PNAS 1985-07, Vol.82 (13), p.4365-4368
• Main Authors: Rinehart, Clifford A., Canellakis, Evangelos S.
• Format: Article
• Language: English
• Subjects: Amino acids; Amino Acids - pharmacology; Aminoisobutyric acids; Aminoisobutyric Acids - pharmacology; Analytical, structural and metabolic biochemistry; Animals; Asparagine - analysis; Biological and medical sciences; Cell growth; Cell lines; Cells, Cultured; Enzyme Induction; Enzymes and enzyme inhibitors; Epidermal Growth Factor - pharmacology; Fibroblast growth factors; Fibroblasts; Fibroblasts - drug effects; Fibroblasts - enzymology; Fundamental and applied biological sciences. Psychology; Growth Substances - pharmacology; Insulin; Insulin - pharmacology; Liver Neoplasms, Experimental - enzymology; Lyases; Mice; Nerve Growth Factors - pharmacology; Neurons; NIH 3T3 cells; Ornithine Decarboxylase - biosynthesis; PC12 cells; Platelet-Derived Growth Factor - pharmacology
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.82.13.4365

The polypeptide growth factors, nerve growth factor, epidermal growth factor, and platelet-derived growth factor, as well as insulin do not induce ornithine decarboxylase (L-ornithine carboxy-lyase, EC 4.1.1.17) unless a minimal concentration of an ornithine decarboxylase-inducing amino acid, such as asparagine, is present in the medium. The effects of the growth factors were studied in appropriately responsive cell lines: pheochromocytoma (PC12) cells for nerve and epidermal growth factors, fibroblasts (NIH 3T3) for platelet-derived growth factor, and fibroblasts and hepatoma (KRC-7) cells for insulin. The nonmetabolizable amino acid analog α -aminoisobutyric acid can replace asparagine, indicating that the covalent modification of the inducing amino acid is not necessary for the induction of ornithine decarboxylase by these growth factors. For the same intracellular concentration of the inducing amino acid, the presence of the growth factors induces higher levels of ornithine decarboxylase. The evidence indicates that these growth factors do not induce ornithine decarboxylase by raising the intracellular concentration of amino acids but rather act synergistically with the inducing amino acid. Evidence is provided that the induction of polyamine-dependent growth by these growth factors is mediated by amino acids. The relationship of these results to the A and N amino acid transport systems and to the Na+influxes in relation to growth is discussed.