p38 MAP kinase regulation of oligodendrocyte differentiation with CREB as a potential target.
Despite a substantial understanding of the factors regulating oligodendrocyte differentiation, the signaling mechanisms involved in this process are not well-understood. This study elaborates on the findings (Bhat NR, Zhang P (1997) FASEB J 11:A925; Baron W, Metz B, Bansal R, Hoekstra D, de Vries H (2000) Mol Cell Neurosci 15:314-329) of a role for p38 MAP kinase signaling in oligodendrocyte differentiation and myelin gene expression. When proliferating oligodendrocyte progenitors were switched to a growth factor-free differentiation medium, there was a rapid activation of p38 kinase that correlated with an increased phosphorylation of CREB, a down-stream target and a factor involved in oligodendrocyte differentiation. Addition of forskolin, a known inducer of intracellular c-AMP and of oligodendrocyte differentiation, also stimulated CREB phosphorylation in a p38 kinase dependent way. Pharmacological inhibition of p38 interfered with the morphological and antigenic changes associated with differentiating oligodendrocytes as well as with the developmental and forskolin-induced expression of myelin basic protein, thereby supporting an essential role for p38 MAPK pathway in oligodendrocyte differentiation.
Bhat
Narayan R
NR
Department of Neurosciences, Medical University of South Carolina, 171 Ashley Avenue, Charleston, SC 29425, USA. bhatnr@musc.edu
Zhang
Peisheng
P
Mohanty
Sangeeta B
SB
D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D005576:Colforsin / Q000494:pharmacology; D017362:Cyclic AMP Response Element-Binding Protein / Q000502:physiology*; D004789:Enzyme Activation; D007093:Imidazoles / Q000494:pharmacology; D004676:Myelin Basic Protein / Q000096:biosynthesis; D018991:Myelin Proteolipid Protein / Q000096:biosynthesis; D018992:Myelin-Associated Glycoprotein / Q000096:biosynthesis; D009836:Oligodendroglia / Q000166:cytology* / Q000187:drug effects; D010766:Phosphorylation / Q000187:drug effects; D011725:Pyridines / Q000494:pharmacology; D012333:RNA, Messenger / Q000037:antagonists & inhibitors; D051381:Rats; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000502:physiology*
D017362:Cyclic AMP Response Element-Binding Protein; D007093:Imidazoles; D004676:Myelin Basic Protein; D018991:Myelin Proteolipid Protein; D018992:Myelin-Associated Glycoprotein; D011725:Pyridines; D012333:RNA, Messenger; D005576:Colforsin; D048051:p38 Mitogen-Activated Protein Kinases; C093642:SB 203580