Protein kinase C-e plays a role in neurite outgrowth in response to epidermal growth factor and nerve growth factor in PC12 Cells. Cell Growth Differ

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-a,-b,-g,-d,-e,-m, and-z. For PKC-d,-e, and-z, NGF and EGF exerted differential effects on translocation. Unlike overexpression of PKC-a and-d, overexpression of PKC-e caused enhanced neurite outgrowth in response to NGF. In the PKC-e-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-a and-d. The induction of neurite outgrowth by EGF was inhibited by the MAPK kinase inhibitor PD95098. In cells overexpressing a PKC-e 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-e in neurite outgrowth in PC12 cells, probably via activation of the MAPK pathway