Pairing of forskolin and KCl increases differentiation of immortalized hippocampal neurons in a CREB Serine 133 phosphorylation-dependent and extracellular-regulated protein kinase-independent manner.
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.
Son
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Department of Biochemistry, Hanyang University College of Medicine, 17 Haengdang-dong, Sungdong-gu, 133-791, Seoul, South Korea. hyeonsun@hanyang.ac.kr
Kim
K O
KO
Kim
J S
JS
Chang
M Y
MY
Lee
S H
SH
Lee
Y S
YS
D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects* / Q000502:physiology; D002461:Cell Line, Transformed / Q000187:drug effects* / Q000502:physiology; D005576:Colforsin / Q000494:pharmacology*; D003470:Culture Media / Q000494:pharmacology; D017362:Cyclic AMP Response Element-Binding Protein / Q000187:drug effects* / Q000378:metabolism; D004347:Drug Interactions / Q000502:physiology; D005333:Fetus; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D006624:Hippocampus / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D007150:Immunohistochemistry; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D008869:Microtubule-Associated Proteins / Q000187:drug effects / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000187:drug effects* / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D010641:Phenotype; D010766:Phosphorylation / Q000187:drug effects; D011189:Potassium Chloride / Q000494:pharmacology*; D051381:Rats; D012694:Serine / Q000187:drug effects / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology
D003470:Culture Media; D017362:Cyclic AMP Response Element-Binding Protein; D008869:Microtubule-Associated Proteins; D016222:Fibroblast Growth Factor 2; D005576:Colforsin; D012694:Serine; D011189:Potassium Chloride; D020928:Mitogen-Activated Protein Kinases