Inhibition of protein kinase C activity promotes the neurotrophic action of epidermal and basic fibroblast growth factors.
In primary neuronal cultures the activation of protein kinase C (PKC) by tumor-promoting phorbol esters blocked growth factor-induced neuronal survival and neurite extension. Depletion of PKC markedly facilitated both epidermal growth factor and basic fibroblast growth factor-inducible neurite extension. Inhibition of PKC by H-7 also stimulated neurite extension. These results suggest that down-regulation of PKC in neurons may be required for trophic factor action.
Morrison
R S
RS
Department of Neurosurgery, Albert Einstein College of Medicine/Montefiore Medical Center, Bronx, NY 10467.
Gross
J L
JL
Moskal
J R
JR
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*; D003712:Dendrites / Q000187:drug effects / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D005346:Fibroblast Growth Factors / Q000494:pharmacology*; D007546:Isoquinolines / Q000494:pharmacology; D010703:Phorbol Esters / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D011493:Protein Kinase C / Q000378:metabolism / Q000502:physiology*; D051381:Rats
D004791:Enzyme Inhibitors; D007546:Isoquinolines; D010703:Phorbol Esters; D010879:Piperazines; D005346:Fibroblast Growth Factors; D004815:Epidermal Growth Factor; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D011493:Protein Kinase C