Mitogen-activated protein kinase activated protein kinase 2 (MK2) participates in p38 MAPK regulated control of oligodendrocyte differentiation
| Autor: | Walter E. Mushynski, Guillermina Almazan, Jeffery D. Haines, Jun Fang |
|---|---|
| Rok vydání: | 2010 |
| Předmět: |
education.field_of_study
biology Kinase p38 mitogen-activated protein kinases Oligodendrocyte differentiation Oligodendrocyte Myelin basic protein Cell biology Cellular and Molecular Neuroscience medicine.anatomical_structure Neurology Biochemistry Mitogen-activated protein kinase medicine biology.protein Protein kinase A education Myelin transcription factor 1 |
| Zdroj: | Glia. 58:1384-1393 |
| ISSN: | 0894-1491 |
| DOI: | 10.1002/glia.21014 |
| Popis: | The p38 mitogen-activated protein kinases (p38 MAPKs) are a family of kinases that regulate a number of cellular functions including cell migration, proliferation, and differentiation. We have previously reported a role for p38 MAPK in the regulation of oligodendrocyte (OLG) differentiation and Schwann cell myelination. Here, we extend our previous findings by showing that a p38 substrate, mitogen-activated protein kinase activated protein kinase 2 (MK2) is a downstream element of the p38 signaling pathway responsible for effecting OLG differentiation. Inhibition of MK2 activity in oligodendrocyte progenitors (OLPs) using CMPD1 [4-(2′-fluorobiphenyl-4-yl)-N-(4-hydroxyphenyl)-butyramide] blocked the activation of MK2 and resulted in decreased accumulation of myelin-differentiation markers, including myelin-associated glycoprotein (MAG) and myelin basic protein (MBP). We corroborated these findings using a small-interfering RNA to MK2, which decreased the myelin-specific lipid galactosylceramide and MAG. Treatment of cultures with CMPD1 decreased the steady state levels of mRNA encoding myelin transcription factor 1 (Myt1), MAG, MBP, and Opalin, a transmembrane sialylglycoprotein expressed in oligodendrocytes. In contrast, increases were observed in the mRNA levels of OLG transcriptional repressors, including transcription factor 4 (Tcf4), Notch1, and inhibitor of differentiation 2 (Id2). Furthermore, we found that the predominantly expressed isoform of p38 in OLGs, p38α, and MK2 can form coimmunoprecipitable complexes in OLPs and OLGs. Our results demonstrate that the p38-MK2 pathway is a component of the signaling cascade regulating OLG differentiation. © 2010 Wiley-Liss, Inc. |
| Databáze: | OpenAIRE |
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