Stimulation of vgf gene expression by NGF is mediated through multiple signal transduction pathways involving protein phosphorylation

Abstract

The vgf gene encodes one of the most rapidly induced neuronal mRNAs identified in NGF-treated PC12 cells. Maximal inhibition of VGF mRNA induction was achieved using K-252a, an inhibitor of the NGF-receptor Trk tyrosine kinase, and by mutating both Y490 (SHC association site) and Y785 (PLC-γ1 association site) of Trk. Inhibitors of the NGF-activated protein kinase N (PKN) were found to partially and in some cases transiently block VGF induction by NGF while in PKA-deficient PC12 cells, VGF induction by NGF was comparable to that observed in parental PC12 cells. The binding of NGF to Trk therefore activates redundant signal transduction pathways which converge to regulate vgf gene expression.