Overexpression of atypical PKC in PC12 cells enhances NGF-responsiveness and survival through an NF-κB dependent pathway

Removal of atypical PKC blocks NGF-induced differentiation of PC12 cells.(1) We now examine the consequences that overexpression of atypical PKCs had upon NGF responses. PC12 cells were stably transfected with either PKC-l or PKC-zeta. Overexpression of atypical PKCs markedly enhanced NGF-induced neurite outgrowth as well as enhanced NGF-stimulated JNK kinase, Cotransfection of HA-JNK1 along with increasing concentrations of PKC-l, resulted in dose-dependent phosphorylation of GST c-Jun (1-79). NGF treatment of PC12 cells resulted in activation of NF-kappa B, In comparison, overexpression of atypical PKC-l was by itself sufficient to activate NF-kappa B and shift the kinetics of NGF-induced kappa B activity. Furthermore, transfection of full-length antisense PKC-l blocked basal and NGF-stimulated NF-kappa B. Differentiated and undifferentiated PC12 cells overexpressing atypical PKC-l were protected from serum deprivation-induced cell death. Collectively, these findings demonstrate that atypical PKC-l lies in a pathway that regulates NF-kappa B and contributes to both neurotrophin-mediated differentiation and survival signaling.