title: K-252a: a specific inhibitor of the action of nerve growth factor on PC 12 cells.
abstract: 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.
authors.affiliation: Section on Growth Factors, National Institutes of Child Health and Human Development, Bethesda, Maryland 20892.
authors.forename: S
authors.initials: S
authors.lastname: Koizumi
authors.forename: M L
authors.initials: ML
authors.lastname: Contreras
authors.forename: Y
authors.initials: Y
authors.lastname: Matsuda
authors.forename: T
authors.initials: T
authors.lastname: Hama
authors.forename: P
authors.initials: P
authors.lastname: Lazarovici
authors.forename: G
authors.initials: G
authors.lastname: Guroff
mesh_terms: D000310:Adrenal Gland Neoplasms / Q000378:metabolism*; D002227:Carbazoles / Q000494:pharmacology*; D026121:Indole Alkaloids; D009414:Nerve Growth Factors / Q000037:antagonists & inhibitors*; D010673:Pheochromocytoma / Q000378:metabolism*
chemical_list: D002227:Carbazoles; D026121:Indole Alkaloids; D009414:Nerve Growth Factors; C049985:staurosporine aglycone