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-indepen-dent signal transduction in PC12 cells is phospholipase C-γ that generates the second messengers dia-cylglycerol 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-trispho-sphate-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.
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Abbreviations
- DAG:
-
diacylglycerol
- dbcAMP:
-
dibutyryl-cAMP
- DMEM:
-
Dulbecco’s modified Eagle medium
- ERK:
-
extracellular signal-regulated kinase
- IP3:
-
inositol-trisphosphate
- MAPK:
-
mitogen-acti-vated protein kinase
- MEK:
-
MAPK/ERK kinase
- NGF:
-
nerve growth factor
- PI3K:
-
phosphatidylinositol 3-kinase
- PIP2:
-
phosphatidylinositol-bisphosphate
- PKA:
-
protein kinase A
- PKC:
-
protein kinase C
- PLC:
-
phospholipase C
- SNT:
-
suc-associated neurotrophic factor-induced tyrosine-phosphorylated target
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Kiss, K., Salamon, S., Törőcsik, B. et al. Role Of Phospholipase C-γ in NGF-Stimulated Differentiation and Gene Induction. BIOLOGIA FUTURA 57, 147–155 (2006). https://doi.org/10.1556/ABiol.57.2006.2.2
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DOI: https://doi.org/10.1556/ABiol.57.2006.2.2