STIMULATION OF VGF GENE-EXPRESSION BY NGF IS MEDIATED THROUGH MULTIPLE SIGNAL-TRANSDUCTION PATHWAYS INVOLVING PROTEIN-PHOSPHORYLATION

The vgf gene encodes one of the most rapidly induced neuronal mRNAs id entified in NGF-treated PC12 cells, Maximal inhibition of VGF mRNA ind uction 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-gamma l association site) of Trk. Inhibitors of the NGF-act ivated protein kinase N (PKN) were found to partially and in some case s transiently block VGF induction by NGF while in PKA-deficient PC12 c ells, VGF induction by NGF was comparable to that observed in parental PC12 cells, The binding of NGF to Trk therefore activates redundant s ignal transduction pathways which converge to regulate vgf gene expres sion,