Involvement of MAP kinase in the cyclic AMP induction of myelin basic protein gene expression.
Cyclic AMP is involved in the differentiation of oligodendrocyte and Schwann cell progenitors into mature myelin producing cells. The involvement of MAP kinases in this pathway was investigated in the D6P2T cell line. This cell line can be induced to display a differentiated phenotype characterized by myelin basic protein gene expression by increased cyclic AMP. Blocking MAP kinase activity with inhibitors of the activating kinase, MEK, by expression of a dominant negative MAP kinase or by expression of the MAP kinase inactivating phosphatase Mkp-1 all blocked the activation of the myelin basic protein promoter in D6P2T cells. In addition, blocking MAP kinase activation during differentiation of an oligodendrocyte-like cell line, CG4, also leads to inhibition of MBP expression. These findings suggest a role for MAP kinase in the cyclic AMP stimulated expression of the myelin basic protein gene during differentiation.
Clark
R
R
Department of Biochemistry and Molecular Biology, University of South Dakota School of Medicine, Vermillion 57069, USA.
Stewart
M
M
Miskimins
W K
WK
Miskimins
R
R
D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism*; D018797:Cell Cycle Proteins; D002454:Cell Differentiation / Q000502:physiology; D002460:Cell Line; D000242:Cyclic AMP / Q000502:physiology*; D054638:Dual Specificity Phosphatase 1; D004789:Enzyme Activation; D005786:Gene Expression Regulation / Q000502:physiology*; D017874:Immediate-Early Proteins / Q000378:metabolism; D004676:Myelin Basic Protein / Q000235:genetics*; D009836:Oligodendroglia / Q000166:cytology; D010749:Phosphoprotein Phosphatases; D011401:Promoter Regions, Genetic; D054645:Protein Phosphatase 1; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism
D018797:Cell Cycle Proteins; D017874:Immediate-Early Proteins; D004676:Myelin Basic Protein; D000242:Cyclic AMP; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D010749:Phosphoprotein Phosphatases; D054645:Protein Phosphatase 1; D054638:Dual Specificity Phosphatase 1; D017027:Protein Tyrosine Phosphatases