The selective protein kinase C inhibitor GF 109203X inhibits phorbol ester-induced morphological and functional differentiation of SH-SY5Y human neuroblastoma cells.

Abstract	Previous attempts to inhibit the phorbol ester 12-O-tetradecanoyl phorbol 13-acetate (TPA) -induced differentiation of SH-SY5Y neuroblastoma cells by non-specific inhibitors of protein kinases have failed. In the present study we have used the bisindolylmaleimide GF 109203X, which is a potent and selective inhibitor of protein kinase C (PKC). GF 109203X effectively antagonized TPA-stimulated phosphorylation of an endogenous 80 kDa PKC substrate. The compound blocked neurite outgrowth and rounding up of cells induced by the phorbol ester. In addition, GF 109203X completely inhibited TPA-induced increase in cellular content of noradrenaline as well as stimulation of expression of neuropeptide Y, growth-associated protein-43 and c-fos proto-oncogene mRNA by TPA. The inhibition of the TPA-induced effects by GF 109203X was dose-dependent.
Authors	J Heikkilä, A Jalava, K Eriksson
Journal	Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 197 Issue 3 Pg. 1185-93 (Dec 30 1993) ISSN: 0006-291X [Print] United States
PMID	8280132 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References	GAP-43 Protein Indoles MAS1 protein, human Maleimides Membrane Glycoproteins Nerve Tissue Proteins Neuropeptide Y Phosphoproteins Proto-Oncogene Mas Proto-Oncogene Proteins c-fos RNA, Messenger Protein Kinase C bisindolylmaleimide I Tetradecanoylphorbol Acetate
Topics	Blotting, Northern Cell Differentiation (drug effects) Cell Line Dose-Response Relationship, Drug GAP-43 Protein Gene Expression (drug effects) Genes, fos (drug effects) Humans Indoles (pharmacology) Kinetics Maleimides (pharmacology) Membrane Glycoproteins (biosynthesis) Molecular Weight Nerve Tissue Proteins (biosynthesis) Neurites (drug effects, physiology, ultrastructure) Neuroblastoma Neuropeptide Y (biosynthesis) Phosphoproteins (biosynthesis, isolation & purification, metabolism) Phosphorylation Protein Kinase C (antagonists & inhibitors) Proto-Oncogene Mas Proto-Oncogene Proteins c-fos (biosynthesis) RNA, Messenger (analysis, drug effects, metabolism) Tetradecanoylphorbol Acetate (pharmacology) Tumor Cells, Cultured

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