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Publication : p38 MAPK-induced nuclear factor-kappaB activity is required for skeletal muscle differentiation: role of interleukin-6.

First Author  Baeza-Raja B Year  2004
Journal  Mol Biol Cell Volume  15
Issue  4 Pages  2013-26
PubMed ID  14767066 Mgi Jnum  J:90016
Mgi Id  MGI:3042312 Doi  10.1091/mbc.E03-08-0585
Citation  Baeza-Raja B, et al. (2004) p38 MAPK-induced nuclear factor-kappaB activity is required for skeletal muscle differentiation: role of interleukin-6. Mol Biol Cell 15(4):2013-26
abstractText  p38 MAPK and nuclear factor-kappaB (NF-kappaB) signaling pathways have been implicated in the control of skeletal myogenesis. However, although p38 is recognized as a potent activator of myoblast differentiation, the role of NF-kappaB remains controversial. Here, we show that p38 is activated only in differentiating myocytes, whereas NF-kappaB activity is present both in proliferation and differentiation stages. NF-kappaB activation was found to be dependent on p38 activity during differentiation, being NF-kappaB an effector of p38, thus providing a novel mechanism for the promyogenic effect of p38. Activation of p38 in C2C12 cells induced the activity of NF-kappaB, in a dual way: first, by reducing IkappaBalpha levels and inducing NF-kappaB-DNA binding activity and, second, by potentiating the transactivating activity of p65-NF-kappaB. Finally, we show that interleukin (IL)-6 expression is induced in C2C12 differentiating myoblasts, in a p38- and NF-kappaB-dependent manner. Interference of IL-6 mRNA reduced, whereas its overexpression increased, the extent of myogenic differentiation; moreover, addition of IL-6 was able to rescue significantly the negative effect of NF-kappaB inhibition on this process. This study provides the first evidence of a crosstalk between p38 MAPK and NF-kappaB signaling pathways during myogenesis, with IL-6 being one of the effectors of this promyogenic mechanism.
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