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) isof orms in the differentiation of PC12 cells in response to nerve growth facto r (NGF) and epidermal growth factor (EGF), PC12 cells express PKC-alpha, -b eta, -gamma, -delta, -epsilon, -mu, and -xi, For PKC-epsilon, -E, and -xi, NGF and EGF exerted differential effects on translocation. Unlike overexpre ssion of PKC-alpha and -delta, overexpression of PKC-epsilon caused enhance d neurite outgrowth in response to NGF. In the PKC-epsilon-overexpressing c ells, EGF also dramatically induced neurite outgrowth, arrested cell prolif eration, and induced a sustained phosphorylation of mitogen-activated prote in kinase (MAPK), in contrast to its mitogenic effects on control cells or cells overexpressing PKC-alpha and -delta. The induction of neurite outgrow th by EGF was inhibited by the MAPK kinase inhibitor PD95098. In cells over expressing a PKC-epsilon dominant negative mutant, NGF induced reduced neur ite outgrowth and a more transient phosphorylation of MAPK than in controls . Our results suggest an important role for PKC-epsilon in neurite outgrowt h in PC12 cells, probably via activation of the MAPK pathway.