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Journal of Neuroscience, Vol 8, 715-721, Copyright © 1988 by Society for Neuroscience
K-252a: a specific inhibitor of the action of nerve growth factor on PC 12 cells
S Koizumi, ML Contreras, Y Matsuda, T Hama, P Lazarovici and G Guroff
Section on Growth Factors, National Institutes of Child Health and Human Development, Bethesda, Maryland 20892.
K-252a, a kinase inhibitor isolated from the culture broth of Nocardiopsis
sp., selectively inhibits the actions of nerve growth factor (NGF) on PC 12
cells. At a concentration of 200 nM, K-252a prevents neurite generation
initiated by NGF, but not neurite generation produced by fibroblast growth
factor or outgrowth produced by dibutyryl cAMP. K-252a also inhibits the
induction of ornithine decarboxylase by NGF, but stimulates ornithine
decarboxylase induction by epidermal growth factor. Stimulation of
phosphatidylinositol breakdown by NGF was similarly inhibited by K-252a,
while stimulation by epidermal growth factor was enhanced. The NGF-induced
decrease in the phosphorylation of a soluble protein, Nsp 100, was
prevented by K- 252a. K-252a blocks the NGF-induced heterodown-regulation
of the epidermal growth factor receptor, but not the epidermal growth
factor- induced homodown-regulation of the epidermal growth factor
receptor. K- 252a, then, provides a new tool for the dissection and study
of NGF- requiring processes.
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