Differentiation of immature oligodendrocytes is regulated by phosphorylation of cyclic AMP-response element binding protein by a protein kinase C signaling cascade

Previous experiments showed that the expression and phosphorylation levels of cyclic AMP‐response element binding protein (CREB) are important factors that regulate oligodendrocyte differentiation. The present study was designed to determine whether CREB phosphorylation advances oligodendrocyte diff...

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Published in:Journal of neuroscience research 2005-06, Vol.80 (6), p.767-776
Main Authors: Shiga, Hatsuki, Yamane, Yukako, Kubo, Minoru, Sakurai, Yoko, Asou, Hiroaki, Ito, Etsuro
Format: Article
Language:English
Subjects:
A2B5
Animals
Blotting, Western
Brain - cytology
Brain - metabolism
Cell Differentiation - physiology
Cells, Cultured
Cyclic AMP Response Element-Binding Protein - metabolism
Cyclic AMP-Dependent Protein Kinases - metabolism
Enzyme Activation - physiology
Immunohistochemistry
MAP Kinase Signaling System - physiology
myelin basic protein (MBP)
Oligodendroglia - cytology
Oligodendroglia - metabolism
Phosphorylation
protein kinase A (PKA)
Protein Kinase C - metabolism
Rats
Rats, Wistar
Stem Cells - metabolism
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Summary:Previous experiments showed that the expression and phosphorylation levels of cyclic AMP‐response element binding protein (CREB) are important factors that regulate oligodendrocyte differentiation. The present study was designed to determine whether CREB phosphorylation advances oligodendrocyte differentiation or vice versa and to identify the protein kinase that primarily regulates CREB phosphorylation. We examined the expression and phosphorylation levels of CREB in developing oligodendrocytes at a specific differentiation stage by double‐immunocytochemical staining with specific differentiation markers and antibody for phosphorylated CREB. We found that the CREB expression level increased along oligodendrocyte differentiation, and that its phosphorylated level was highest in immature oligodendrocytes. We also showed that CREB phosphorylation was regulated principally by protein kinase C (PKC) activity in immature oligodendrocytes. Our findings suggest that CREB phosphorylation is dependent on a PKC signaling cascade, and this phosphorylation activates CREB‐mediated transcription and advances the differentiation of immature to mature oligodendrocytes. © 2005 Wiley‐Liss, Inc.
ISSN:0360-4012
1097-4547
DOI:10.1002/jnr.20513