A PKC beta isoform mediates phorbol ester-induced activation of Erk1/2 andexpression of neuronal differentiation genes in neuroblastoma cells

Protein kinase C (PKC) activation induces neuronal differentiation of SH-SY 5Y neuroblastoma cells. This study examines the role of PKC beta isoforms i n this process. The PKC beta- specific inhibitor LY379196 had no effect on 12-O-tetradecanoylphorbol 13-acetate (TPA)-induced neurite outgrowth from S H-SV5Y neuroblastoma cells. On the other hand, PKC beta inhibition suppress ed the TPA-stimulated increase in neuropeptide Y mRNA, activation of neurop eptide V gene promoter elements, and phosphorylation of Erk1/2. The TPA-ind uced increase in neuropeptide Y expression was also inhibited by the MEK in hibitor PD98059. These data indicate that activation of a PKC beta isoform, through a pathway involving Erk1/2, leads to increased expression of neuro nal differentiation genes in neuroblastoma cells. (C) 2001 Federation of Eu ropean Biochemical Societies. Published by Elsevier Science B.V. All rights reserved.