ROLE OF PHOSPHOLIPASE C- γ IN NGF-STIMULATED DIFFERENTIATION AND GENE INDUCTION

Kiss, K. and Salamon, Sz. and Törőcsik, B. and Szeberényi, J. (2006) ROLE OF PHOSPHOLIPASE C- γ IN NGF-STIMULATED DIFFERENTIATION AND GENE INDUCTION. Acta Biologica Hungarica, 57 (2). pp. 147-155. ISSN 0236-5383

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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-g 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, zif268 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-g-mediated pathways are inhibited. The phospholipase C-g 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.

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