Role of phospholipase C-gamma in NGF-stimulated differentiation and gene induction.
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-gamma 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-gamma-mediated pathways are inhibited. The phospholipase C-gamma 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.
Kiss
K
K
Department of Medical Biology, Medical School, University of Pécs, Szigeti u. 12, H-7624 Pécs, Hungary.
Salamon
Sz
S
Töröcsik
B
B
Szeberényi
J
J
D000818:Animals; D002454:Cell Differentiation / Q000502:physiology*; D004963:Estrenes / Q000378:metabolism; D005786:Gene Expression Regulation; D015544:Inositol 1,4,5-Trisphosphate / Q000037:antagonists & inhibitors; D047028:Macrocyclic Compounds / Q000378:metabolism; D020932:Nerve Growth Factor / Q000378:metabolism*; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D010080:Oxazoles / Q000378:metabolism; D016716:PC12 Cells; D010726:Phosphodiesterase Inhibitors / Q000378:metabolism; D051966:Phospholipase C gamma / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011760:Pyrrolidinones / Q000378:metabolism; D051381:Rats; D015398:Signal Transduction / Q000502:physiology; D015533:Transcriptional Activation
D004963:Estrenes; D047028:Macrocyclic Compounds; D010080:Oxazoles; D010726:Phosphodiesterase Inhibitors; D011760:Pyrrolidinones; C511704:xestospongin C; C060229:1-(6-((3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione; D015544:Inositol 1,4,5-Trisphosphate; D020932:Nerve Growth Factor; D051966:Phospholipase C gamma