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. 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-ζ. Overexpression of atypical PKCs markedly enhanced NGFinduced neurite outgrowth as well as enhanced NGFstimulated JNK kinase. Cotransfection of HA-JNK1 along with increasing concentrations of PKC-l, resulted in dosedependent phosphorylation of GST c-Jun (1-79). NGF treatment of PC12 cells resulted in activation of NF-κB. In comparison, overexpression of atypical PKC-l was by itself sufficient to activate NF-κB and shift the kinetics of NGFinduced κB activity. Furthermore, transfection of full-length antisense PKC-l blocked basal and NGF-stimulated NF-κB. Differentiated and undifferentiated PC12 cells overexpressing atypical PKC-l were protected from serum deprivationinduced cell death. Collectively, these findings demonstrate that atypical PKC-l lies in a pathway that regulates NF-κB and contributes to both neurotrophin-mediated differentiation and survival signaling. [ABSTRACT FROM AUTHOR]