TGF-β-activated Kinase 1 (TAK1) and Apoptosis Signal-regulating Kinase 1 (ASK1) Interact with the Promyogenic Receptor Cdo to Promote Myogenic Differentiation via Activation of p38MAPK Pathway
Copyright policy )TGF-β-activated Kinase 1 (TAK1) and Apoptosis Signal-regulating Kinase 1 (ASK1) Interact with the Promyogenic Receptor Cdo to Promote Myogenic Differentiation via Activation of p38MAPK Pathway
p38MAPK plays an essential role in the transition of myoblasts to differentiated myotubes through the activation of MyoD family transcription factors. A promyogenic cell surface molecule, Cdo, promotes myogenic differentiation mainly through activation of the p38MAPK pathway. Two MAP3Ks, TAK1 and ASK1, can activate p38MAPK via MKK6 in various cell systems. Moreover TAK1 has been shown to promote myogenic differentiation via p38MAPK activation. In this study, we hypothesized that TAK1 and ASK1 might function as MAP3Ks in Cdo-mediated p38MAPK activation during myoblast differentiation. Both ASK1 and TAK1 were expressed in myoblasts and interacted with the cytoplasmic tail of Cdo and a scaffold protein, JLP. The depletion of TAK1 or ASK1 in C2C12 cells decreased myoblast differentiation, whereas overexpression of TAK1 or ASK1 in C2C12 cells enhanced myotube formation. In agreement with this, overexpression of ASK1 or TAK1 resulted in enhanced p38MAPK activation, and their knockdown inhibited p38MAPK in C2C12 cells. Overexpression of TAK1 or ASK1 in Cdo(-/-) myoblasts and Cdo-depleted C2C12 cells restored p38MAPK activation as well as myotube formation. Furthermore, ASK1 and TAK1 compensated for each other in p38MAPK activation and myoblast differentiation. Taken together, these findings suggest that ASK1 and TAK1 function as MAP3Ks in Cdo-mediated p38MAPK activation to promote myogenic differentiation.
- Sookmyung Women's University Korea (Republic of)
- Sungkyul University Korea (Republic of)
- Sungkyunkwan University Korea (Republic of)
- Samsung (South Korea) Korea (Republic of)
MAP Kinase Signaling System, Muscle Fibers, Skeletal, Cell Differentiation, MAP Kinase Kinase Kinase 5, MAP Kinase Kinase Kinases, Muscle Development, p38 Mitogen-Activated Protein Kinases, Cell Line, Enzyme Activation, Myoblasts, Gene Knockout Techniques, Mice, Multiprotein Complexes, Animals, Humans, Cell Adhesion Molecules, Cell Proliferation, Protein Binding
MAP Kinase Signaling System, Muscle Fibers, Skeletal, Cell Differentiation, MAP Kinase Kinase Kinase 5, MAP Kinase Kinase Kinases, Muscle Development, p38 Mitogen-Activated Protein Kinases, Cell Line, Enzyme Activation, Myoblasts, Gene Knockout Techniques, Mice, Multiprotein Complexes, Animals, Humans, Cell Adhesion Molecules, Cell Proliferation, Protein Binding
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