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 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.
Shiga
Hatsuki
H
Division of Biological Sciences, Graduate School of Science, Hokkaido University, Kita-ku, Sapporo, Japan.
Yamane
Yukako
Y
Kubo
Minoru
M
Sakurai
Yoko
Y
Asou
Hiroaki
H
Ito
Etsuro
E
D000818:Animals; D015153:Blotting, Western; D001921:Brain / Q000166:cytology / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology*; D002478:Cells, Cultured; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D004789:Enzyme Activation / Q000502:physiology; D007150:Immunohistochemistry; D020935:MAP Kinase Signaling System / Q000502:physiology*; D009836:Oligodendroglia / Q000166:cytology* / Q000378:metabolism*; D010766:Phosphorylation; D011493:Protein Kinase C / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D013234:Stem Cells / Q000378:metabolism
D017362:Cyclic AMP Response Element-Binding Protein; D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C