K-252a inhibits the increase in c-fos transcription and the increase in intracellular calcium produced by nerve growth factor in PC12 cells

• Published in: Journal of neuroscience research Vol. 23; no. 1; p. 1
• Main Authors: Lazarovici, P, Levi, B Z, Lelkes, P I, Koizumi, S, Fujita, K, Matsuda, Y, Ozato, K, Guroff, G
• Format: Journal Article
• Language: English
• Published: United States 01.05.1989
• Subjects: Adrenal Gland Neoplasms; Animals; Calcium - metabolism; Carbazoles - pharmacology; Cell Line; DNA-Binding Proteins - genetics; Indole Alkaloids; Nerve Growth Factors - pharmacology; Nucleic Acid Hybridization; Pheochromocytoma; Protein Kinase C - antagonists & inhibitors; Proto-Oncogene Proteins - genetics; Proto-Oncogene Proteins c-fos; Proto-Oncogenes - drug effects; RNA, Messenger - drug effects; RNA, Messenger - genetics; RNA, Neoplasm - genetics; RNA, Neoplasm - isolation & purification; Transcription, Genetic - drug effects
• ISSN: 0360-4012
• DOI: 10.1002/jnr.490230102

K-252a, a kinase inhibitor isolated from the culture broth of Nocardiopsis sp., selectively inhibits, in a dose- and time-dependent fashion, the increased transcription of the protooncogene c-fos induced by nerve growth factor in PC12 cells. Induction of c-fos by epidermal growth factor, A23187, dBcAMP, or TPA in the same cells is not affected. Pretreatment with K-252a for 30 min results in a complete inhibition of the nerve growth factor-induced increase in intracellular calcium. Increases in intracellular calcium induced by carbachol or by high K+ are not altered. K-252a derivatives selective for the inhibition of various known kinases were used to inhibit the nerve growth factor-dependent induction of c-fos mRNA, the nerve growth factor-dependent increase in intracellular calcium levels, and the nerve growth factor-dependent outgrowth of neurites. K-252a is the most effective inhibitor of all three of these actions of nerve growth factor. The possible mechanisms by which K-252a acts on PC12 cells are considered in the light of the characteristics of the inhibitions seen here.