K252a-potentiation of EGF-induced neurite outgrowth from PC12 cells is not mimicked or blocked by other protein kinase activators or inhibitors.
Epidermal growth factor (EGF) has recently been shown to cause certain strains of PC12 cells to extend short neurites. This EGF-induced differentiation of PC12 was found to be potentiated by the protein kinase inhibitor, K252a, in that PC12 cells treated with both EGF and K252a extended long branched neurites similar to those induced by nerve growth factor (NGF). As reported here no other protein kinase inhibitor or activator mimicked or blocked the effect of K252a on EGF-induced PC12 differentiation. Cyclic adenosine 3',5'-monophosphate (cAMP) also potentiated EGF-induced neurite outgrowth from PC12 cells, but the mechanism of this potentiation was different from that of K252a. Cells that had been exposed to EGF and then stripped of their neurons extended neurites again when retreated with EGF in the absence of RNA synthesis or when treated with NGF in the absence of RNA synthesis. Thus EGF can prime PC12 cells for either EGF or for NGF, a finding that further suggests that EGF and NGF use similar signaling pathways to induced neuronal differentiation of PC12.
Wu
C F
CF
Department of Biological Chemistry, School of Medicine, University of California, Los Angeles 90024, USA.
Howard
B D
BD
D000818:Animals; D003994:Bucladesine / Q000494:pharmacology; D002227:Carbazoles / Q000494:pharmacology*; D002454:Cell Differentiation; D004357:Drug Synergism; D004789:Enzyme Activation; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D026121:Indole Alkaloids; D008934:Mitogens / Q000494:pharmacology; D016501:Neurites / Q000187:drug effects* / Q000502:physiology*; D016716:PC12 Cells; D010750:Phosphoproteins / Q000378:metabolism; D047428:Protein Kinase Inhibitors; D011494:Protein Kinases / Q000378:metabolism*; D051381:Rats; D013997:Time Factors
D002227:Carbazoles; D026121:Indole Alkaloids; D008934:Mitogens; D010750:Phosphoproteins; D047428:Protein Kinase Inhibitors; D004815:Epidermal Growth Factor; D003994:Bucladesine; C049985:staurosporine aglycone; D011494:Protein Kinases