Protein kinase inhibitors block neurite outgrowth from explants of goldfish retina.
A role for protein phosphorylation in the process of neurite outgrowth has been inferred from many studies of the effects of protein kinase inhibitors and activators on cultured neurotumor cells and primary neuronal cells from developing brain or ganglia. Here we re-examine this issue, using a culture system derived from a fully differentiated neuronal system undergoing axonal regeneration--the explanted goldfish retina following optic nerve crush. Of the relatively non-selective protein kinase inhibitors employed, H7, staurosporine and K252a were found to block neurite outgrowth, whereas HA1004 had no effect, a result which appears to rule out a critical role for protein kinase A. The more selective protein kinase C inhibitors, sphingosine, calphostin C and Ro-31-8220 were all inhibitory, as was prolonged treatment with phorbol ester and the protein phosphatase inhibitor okadaic acid. These results are in support of a role for protein kinase C in axonal regrowth.
Heacock
A M
AM
Neuroscience Laboratory, University of Michigan, Ann Arbor 48104-1687, USA.
Agranoff
B W
BW
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / Q000494:pharmacology; D000818:Animals; D002227:Carbazoles / Q000494:pharmacology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors; D006054:Goldfish; D026121:Indole Alkaloids; D009409:Nerve Crush; D016501:Neurites / Q000187:drug effects* / Q000502:physiology* / Q000648:ultrastructure; D019319:Okadaic Acid / Q000494:pharmacology; D009900:Optic Nerve / Q000648:ultrastructure; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D047428:Protein Kinase Inhibitors; D012160:Retina / Q000648:ultrastructure*; D013110:Sphingosine / Q000494:pharmacology; D019311:Staurosporine / Q000494:pharmacology
D002227:Carbazoles; D026121:Indole Alkaloids; D047428:Protein Kinase Inhibitors; D019319:Okadaic Acid; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; C049985:staurosporine aglycone; D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C; D019311:Staurosporine; D013110:Sphingosine