SELECTIVE TRANSLOCATION OF PROTEIN-KINASE C-DELTA IN PC12 CELLS DURING NERVE GROWTH FACTOR-INDUCED NEURITOGENESIS

The specific intracellular signals initiated by nerve growth factor (N GF) that lead to neurite formation in PC12 rat pheochromocytoma cells are as of yet unclear. Protein kinase C-delta (PKC delta) is transloca ted from the soluble to the particulate subcellular fraction during NG F-induced-neuritogenesis; however, this does not occur after treatment with the epidermal growth factor, which is mitogenic but does not ind uce neurite formation. PC12 cells also contain both Ca2+-sensitive and Ca2+-independent PKC enzymatic activities, and express mRNA and immun oreactive proteins corresponding to the PKC isoforms alpha, beta, delt a, epsilon, and zeta. There are transient decreases in the levels of i mmunoreactive PKCs alpha, beta, and epsilon after 1-3 days of NGF trea tment, and after 7 days there is a 2.5-fold increase in the level of P KC alpha, and a 1.8-fold increase in total cellular PKC activity. NGF- induced PC12 cell neuritogenesis is enhanced by 12-O-tetradecanoyl pho rbol-13-acetate (TPA) in a TPA dose- and time-dependent manner, and th is differentiation coincides with abrogation of the down-regulation of PKC delta and other PKC isoforms, when the cells are treated with TPA . Thus a selective activation of PKC delta may play a role in neuritog enic signals in PC12 cells.