Mitogen‐activated protein kinase activated protein kinase 2 (MK2) participates in p38 MAPK regulated control of oligodendrocyte differentiation

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.