A functional role for ERK in gene induction, but not in neurite outgrowth in differentiating neuroblastoma cells

The human neuroblastoma cell line SH-SY5Y can differentiate into a function al sympathetic neuronal phenotype when treated with low concentrations of t he phorbol eater 12-O-tetradecanoylphorbol-13-acetate (TPA) in the presence of serum or defined growth factors, When TrkA is introduced into the cells , NGF also induces differentiation. In both cases, protein kinase C (PKC) i s pivotal for induction and maintenance of the differentiated phenotype. We have recently shown that PKC activity is needed to enable the MAPK ERK to accumulate in the nucleus of SH-SY5Y cells and hence activate transcription , To find out whether this could be one reason for the PKC dependency in th e differentiation process we have investigated the role of ERK during neuro nal differentiation of these cells. The results show that ERK was needed fo r full upregulation of the neuronal marker genes NPY and GAP-43. However, E RK activity was not necessary for TPA-induced neurite formation. Neither wa s activation of ERK sufficient to promote neurite outgrowth. The results cl early show that there was no correlation between nuclear ERK activity, meas ured as SRE transactivation, and neurite formation in TPA-differentiated SH -SY5Y neuroblastoma cells. (C) 2001 Academic Press.