Protein kinase C-epsilon plays a role in neurite outgrowth in response to epidermal growth factor and nerve growth factor in PC12 cells.
In this study, we examined the role of specific protein kinase C (PKC) isoforms in the differentiation of PC12 cells in response to nerve growth factor (NGF) and epidermal growth factor (EGF). PC12 cells express PKC-alpha, -beta, -gamma, -delta, -epsilon, -mu, and -zeta. For PKC-delta, -epsilon, and -zeta, NGF and EGF exerted differential effects on translocation. Unlike overexpression of PKC-alpha and -delta, overexpression of PKC-epsilon caused enhanced neurite outgrowth in response to NGF. In the PKC-epsilon-overexpressing cells, EGF also dramatically induced neurite outgrowth, arrested cell proliferation, and induced a sustained phosphorylation of mitogen-activated protein kinase (MAPK), in contrast to its mitogenic effects on control cells or cells overexpressing PKC-alpha and -delta. The induction of neurite outgrowth by EGF was inhibited by the MAPK kinase inhibitor PD95098. In cells overexpressing a PKC-epsilon dominant negative mutant, NGF induced reduced neurite outgrowth and a more transient phosphorylation of MAPK than in controls. Our results suggest an important role for PKC-epsilon in neurite outgrowth in PC12 cells, probably via activation of the MAPK pathway.
Brodie
C
C
Molecular Mechanisms of Tumor Promotion Section, National Cancer Institute, NIH, Bethesda, Maryland 20892, USA.
Bogi
K
K
Acs
P
P
Lazarovici
P
P
Petrovics
G
G
Anderson
W B
WB
Blumberg
P M
PM
D000818:Animals; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism; D002455:Cell Division; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004815:Epidermal Growth Factor / Q000502:physiology*; D005419:Flavonoids / Q000494:pharmacology; D015151:Immunoblotting; D051379:Mice; D016296:Mutagenesis; D009414:Nerve Growth Factors / Q000502:physiology*; D016501:Neurites / Q000187:drug effects / Q000502:physiology*; D016716:PC12 Cells; D010766:Phosphorylation; D011493:Protein Kinase C / Q000502:physiology*; D051381:Rats; D013997:Time Factors; D014178:Translocation, Genetic
D004791:Enzyme Inhibitors; D005419:Flavonoids; D009414:Nerve Growth Factors; D004815:Epidermal Growth Factor; D011493:Protein Kinase C; D017871:Calcium-Calmodulin-Dependent Protein Kinases; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one