Role of phospholipase C-γ in NGF-stimulated differentiation and gene induction

K. Kiss, Sz Salamon, B. Töröcsik, J. Szeberényi

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

The PC12 phaeochromocytoma cell line provides a useful model to study nerve growth factor-induced neuronal differentiation. The central signaling route of this process is mediated by the Ras-dependent extracellular signal-regulated kinase cascade. However, Ras-independent pathways are also stimulated by nerve growth factor and may contribute to differentiation signaling. One mediator for Ras-independent signal transduction in PC12 cells is phospholipase C-γ that generates the second messengers diacylglycerol and inositol-trisphosphate. To probe the possible involvement of this enzyme in nerve growth factor-promoted differentiation, we used the phospholipase C inhibitor U73122 and the inositol-trisphosphate-receptor inhibitor Xestospongin C. Our results show that both chemicals block nerve growth factor-promoted neurite outgrowth, but the blockage of phospholipase C does not inhibit nerve growth factor-induced expression of c-fos, zif 268 and transin genes. In addition, induction of these genes by nerve growth factor plus dibutyryl-cAMP is comparable in wild-type PC12 cells as well as in cells in which both Ras- and phospholipase C-γ-mediated pathways are inhibited. The phospholipase C-γ pathway thus belongs to those nerve growth factor receptor-originated signaling routes that contribute to the biological response of PC12 cells to nerve growth factor, but its gene activating potential does not have a major role in its neuritogenic effect.

Original languageEnglish
Pages (from-to)147-155
Number of pages9
JournalActa biologica Hungarica
Volume57
Issue number2
DOIs
Publication statusPublished - Jul 25 2006

Keywords

  • Gene induction
  • Nerve growth factor
  • Neuronal differentiation
  • PC12 cells
  • Phospholipase C-γ

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Environmental Science(all)
  • Neurology

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