PMID:22337877

Citation	Tran, P, Ho, SM, Kim, BG, Vuong, TA, Leem, YE, Bae, GU and Kang, JS (2012) 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. J. Biol. Chem. 287:11602-15
Abstract	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.
Links	PubMed PMC3320910 Online version:10.1074/jbc.M112.351601
Keywords	Animals; Cell Adhesion Molecules/genetics; Cell Adhesion Molecules/metabolism; Cell Differentiation; Cell Line; Cell Proliferation; Enzyme Activation; Gene Knockout Techniques; Humans; MAP Kinase Kinase Kinase 5/genetics; MAP Kinase Kinase Kinase 5/metabolism; MAP Kinase Kinase Kinases/genetics; MAP Kinase Kinase Kinases/metabolism; MAP Kinase Signaling System; Mice; Multiprotein Complexes/genetics; Multiprotein Complexes/metabolism; Muscle Development; Muscle Fibers, Skeletal/cytology; Muscle Fibers, Skeletal/metabolism; Myoblasts/metabolism; Myoblasts/physiology; Protein Binding; p38 Mitogen-Activated Protein Kinases/metabolism
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
MOUSE:M3K5	involved_in	GO:0045663: positive regulation of myoblast differentiation	ECO:0000314: direct assay evidence used in manual assertion		P		Seeded From UniProt	complete
MOUSE:M3K5	involved_in	GO:0038066: p38MAPK cascade	ECO:0000270: expression pattern evidence used in manual assertion		P		Seeded From UniProt	complete
MOUSE:M3K5		GO:0045663: positive regulation of myoblast differentiation	ECO:0000314:		P		Fig. 3	complete CACAO 3800
MOUSE:M3K5		GO:0038066: p38MAPK cascade	ECO:0000270:		P		Fig. 4	complete CACAO 3811
MOUSE:NR2C2		GO:0045663: positive regulation of myoblast differentiation	ECO:0000314:		P		Fig. 2	complete CACAO 3801
MOUSE:NR2C2		GO:0038066: p38MAPK cascade	ECO:0000270:		P		Fig. 4	complete CACAO 3812
MOUSE:NR2C2	involved_in	GO:0045663: positive regulation of myoblast differentiation	ECO:0000314: direct assay evidence used in manual assertion		P		Seeded From UniProt	complete
MOUSE:NR2C2	involved_in	GO:0038066: p38MAPK cascade	ECO:0000270: expression pattern evidence used in manual assertion		P		Seeded From UniProt	complete

References

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