Notch signaling suppresses p38 MAPK activity via induction of MKP-1 in myogenesis.
Cross-talks among intracellular signaling pathways are important for the regulation of cell fate decisions and cellular responses to extracellular signals. Both the Notch pathway and the MAPK pathways play important roles in many biological processes, and the Notch pathway has been shown to interact with the ERK-type MAPK pathway. However, its interaction with the other MAPK pathways is unknown. Here we show that Notch signaling activation in C2C12 cells suppresses the activity of p38 MAPK to inhibit myogenesis. Our results show that Notch specifically induces expression of MKP-1, a member of the dual-specificity MAPK phosphatase, which directly inactivates p38 to negatively regulate C2C12 myogenesis. The Notch-induced expression of MKP-1 is shown to depend on RBP-J. Moreover, inhibition of MKP-1 expression by short interfering RNA suppresses p38 inactivation and partially rescues the negative regulation of myogenesis. These results reveal a novel cross-talk between the Notch pathway and the p38 MAPK pathway that is mediated by Notch induction of MKP-1.
Kondoh
Kunio
K
Department of Cell and Developmental Biology, Graduate School of Biostudies, Kyoto University, Kyoto 606-8502, Japan.
Sunadome
Kazunori
K
Nishida
Eisuke
E
D000818:Animals; D018797:Cell Cycle Proteins / Q000235:genetics*; D002460:Cell Line; D018076:DNA, Complementary / Q000235:genetics; D054638:Dual Specificity Phosphatase 1; D004790:Enzyme Induction; D017930:Genes, Reporter; D017874:Immediate-Early Proteins / Q000235:genetics*; D051379:Mice; D024510:Muscle Development / Q000502:physiology*; D010749:Phosphoprotein Phosphatases / Q000235:genetics*; D010957:Plasmids; D054645:Protein Phosphatase 1; D017027:Protein Tyrosine Phosphatases / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D051880:Receptors, Notch / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors*
D018797:Cell Cycle Proteins; D018076:DNA, Complementary; D017874:Immediate-Early Proteins; D012333:RNA, Messenger; D051880:Receptors, Notch; D048051:p38 Mitogen-Activated Protein Kinases; D010749:Phosphoprotein Phosphatases; D054645:Protein Phosphatase 1; D054638:Dual Specificity Phosphatase 1; C517020:Dusp1 protein, mouse; D017027:Protein Tyrosine Phosphatases