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

Exp Cell Res. 2001 Apr 15;265(1):21-30. doi: 10.1006/excr.2001.5163.


The human neuroblastoma cell line SH-SY5Y can differentiate into a functional sympathetic neuronal phenotype when treated with low concentrations of the phorbol ester 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) is 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 the differentiation process we have investigated the role of ERK during neuronal differentiation of these cells. The results show that ERK was needed for full upregulation of the neuronal marker genes NPY and GAP-43. However, ERK activity was not necessary for TPA-induced neurite formation. Neither was activation of ERK sufficient to promote neurite outgrowth. The results clearly show that there was no correlation between nuclear ERK activity, measured as SRE transactivation, and neurite formation in TPA-differentiated SH-SY5Y neuroblastoma cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Calcium-Calmodulin-Dependent Protein Kinases / antagonists & inhibitors
  • Cell Differentiation
  • DNA-Binding Proteins / metabolism
  • Enzyme Activation
  • Enzyme Inhibitors / pharmacology
  • Flavonoids / pharmacology
  • GAP-43 Protein / genetics
  • Gene Expression* / drug effects
  • Humans
  • MAP Kinase Kinase Kinase 1*
  • Mitogen-Activated Protein Kinases / metabolism
  • Mitogen-Activated Protein Kinases / physiology*
  • Mitogens / pharmacology
  • Neurites / physiology*
  • Neuroblastoma
  • Neuropeptide Y / genetics
  • Nuclear Proteins / metabolism
  • Protein-Serine-Threonine Kinases / metabolism
  • Proto-Oncogene Proteins c-fos / genetics
  • Receptor, trkA / genetics
  • Serum Response Factor
  • Tetradecanoylphorbol Acetate / pharmacology
  • Transcription Factors / metabolism
  • Transcription, Genetic
  • Tumor Cells, Cultured
  • ras Proteins / metabolism


  • DNA-Binding Proteins
  • Enzyme Inhibitors
  • Flavonoids
  • GAP-43 Protein
  • Mitogens
  • Neuropeptide Y
  • Nuclear Proteins
  • Proto-Oncogene Proteins c-fos
  • Serum Response Factor
  • Transcription Factors
  • Receptor, trkA
  • Protein-Serine-Threonine Kinases
  • Calcium-Calmodulin-Dependent Protein Kinases
  • Mitogen-Activated Protein Kinases
  • MAP Kinase Kinase Kinase 1
  • MAP3K1 protein, human
  • ras Proteins
  • Tetradecanoylphorbol Acetate
  • 2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one