K-252a inhibits the increase in c-fos transcription and the increase in intracellular calcium produced by nerve growth factor in PC12 cells
- 1 May 1989
- journal article
- research article
- Published by Wiley in Journal of Neuroscience Research
- Vol. 23 (1), 1-8
- https://doi.org/10.1002/jnr.490230102
Abstract
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 calclum. 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.Keywords
This publication has 38 references indexed in Scilit:
- Calcium‐Dependent Nerve Growth Factor‐Stimulated Hydrolysis of Phosphoinositides in PC12 CellsJournal of Neurochemistry, 1987
- DNA sequence analysis of diuron‐resistant mutations in the mitochondrial cytochrome b gene of Saccharomyces cerevisiaeFEBS Letters, 1986
- Regulation of Nerve Growth Factor Action on Nsp100 Phosphorylation in PC12h Cells by CalciumJournal of Neurochemistry, 1986
- Gene Transfer and Molecular Cloning of the Human NGF ReceptorScience, 1986
- Protein kinase C as a component of a nerve growth factor-sensitive phosphorylation system in PC12 cells.Proceedings of the National Academy of Sciences, 1986
- The importance of both early and delayed responses in the biological actions of nerve growth factorTrends in Neurosciences, 1984
- A second messenger required for nerve growth factor biological activity?Nature, 1981
- Nerve growth factor mediates phosphorylation of specific proteinsCell, 1980
- The Nerve Growth Factor: Biochemistry, Synthesis, and Mechanism of ActionAnnual Review of Neuroscience, 1980
- THE NERVE GROWTH FACTOR: PURIFICATION AS A 30,000-MOLECULAR-WEIGHT PROTEINProceedings of the National Academy of Sciences, 1969