Abstract
Although cAMP response element binding protein (CREB)- and extracellular-regulated protein kinase (ERK)-mediated pathways have been linked to each other in neuronal differentiation, involvement of these in hippocampal neuronal cell line has not been defined. Using an immortalized hippocampal cell line, HiB5, we have tried a pairing of forskolin with KCl depolarization, which acts as an ERK and CREB kinase activator in hippocampal neurons, to investigate if an activation of ERK and phosphorylation of CREB at the critical regulatory site, serine 133 might be coupled in differentiation. Differentiation toward a neuronal phenotype was synergistically and markedly increased by the pairing of forskolin and KCl depolarization. The synergistic effect was accompanied by an increase in phosphorylation of CREB Ser-133, but not phosphorylation of ERK, and was not inhibited by MEK inhibitor, PD98059. These findings indicate that phosphorylation of the transcriptional factor CREB may function to facilitate differentiation of HiB5 cells.
MeSH terms
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Animals
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Cell Differentiation / drug effects*
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Cell Differentiation / physiology
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Cell Line, Transformed / drug effects*
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Cell Line, Transformed / physiology
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Colforsin / pharmacology*
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Culture Media / pharmacology
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Cyclic AMP Response Element-Binding Protein / drug effects*
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Cyclic AMP Response Element-Binding Protein / metabolism
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Drug Interactions / physiology
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Fetus
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Fibroblast Growth Factor 2 / pharmacology
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Hippocampus / cytology
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Hippocampus / embryology
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Hippocampus / metabolism
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Immunohistochemistry
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Membrane Potentials / drug effects
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Membrane Potentials / physiology
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Microtubule-Associated Proteins / drug effects
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Microtubule-Associated Proteins / metabolism
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Mitogen-Activated Protein Kinases / drug effects*
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Mitogen-Activated Protein Kinases / metabolism
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Neurons / cytology
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Neurons / drug effects*
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Neurons / metabolism
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Phenotype
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Phosphorylation / drug effects
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Potassium Chloride / pharmacology*
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Rats
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Serine / drug effects
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Serine / metabolism
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Signal Transduction / drug effects
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Signal Transduction / physiology
Substances
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Culture Media
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Cyclic AMP Response Element-Binding Protein
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Microtubule-Associated Proteins
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Fibroblast Growth Factor 2
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Colforsin
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Serine
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Potassium Chloride
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Mitogen-Activated Protein Kinases