Staurosporine induces a neuronal phenotype in SH-SY5Y human neuroblastoma cells that resembles that induced by the phorbol ester 12-O-tetradecanoyl phorbol-13 acetate (TPA).
Treatment of SH-SY5Y human neuroblastoma cells with the protein kinase inhibitor staurosporine, induced both morphological and functional differentiation in these cells. The effects of staurosporine were comparable to those induced by the protein kinase C (PKC) activator, 12-O-tetradecanoyl phorbol 13-acetate (TPA), with respect to induction of neuronal differentiation, i.e. neurite outgrowth, inhibition of DNA synthesis, induction and down-regulation of c-myc protein expression, induction of mRNA for both neuropeptide Y (NPY) and growth associated protein 43 (GAP-43) and stimulation of tyrosine hydroxylase expression. Staurosporine failed to translocate PKC to the membrane fraction or to stimulate phosphorylation of the endogenous PKC substrate M(r) 80,000 (p80). Instead, staurosporine inhibited TPA-induced phosphorylation of p80.
Department of Biochemistry and Pharmacy, Abo Akademi University, Turku, Finland.
A
A
Jalava
J
J
Heikkilä
M
M
Lintunen
K
K
Akerman
S
S
Påhlman
D000470:Alkaloids / Q000494:pharmacology*; D015152:Blotting, Northern; D015153:Blotting, Western; D002454:Cell Differentiation / Q000187:drug effects*; D019922:GAP-43 Protein; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D008562:Membrane Glycoproteins / Q000096:biosynthesis; D009419:Nerve Tissue Proteins / Q000096:biosynthesis; D009474:Neurons / Q000166:cytology / Q000187:drug effects*; D009478:Neuropeptide Y / Q000096:biosynthesis; D010766:Phosphorylation; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis; D019311:Staurosporine; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D014446:Tyrosine 3-Monooxygenase / Q000096:biosynthesis
D000470:Alkaloids; D019922:GAP-43 Protein; D008562:Membrane Glycoproteins; D009419:Nerve Tissue Proteins; D009478:Neuropeptide Y; D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger; D014446:Tyrosine 3-Monooxygenase; D011493:Protein Kinase C; D019311:Staurosporine; D013755:Tetradecanoylphorbol Acetate