p38 mitogen-activated protein kinase up-regulates NF-kappaB transcriptional activation through RelA phosphorylation during stretch-induced myogenesis.
p38 MAPK and nuclear factor-B (NF-B) signaling pathways play an indispensable role in the control of skeletal myogenesis. The specific contribution of these signaling pathways to the response of myoblast to the mechanical stimulation and the molecular mechanisms underlying this response remain unresolved. Using an established in vitro model, we now show that p38 MAP kinase activity regulates the transcriptional activation of NF-kappaB in response to mechanical stimulation of myoblasts. Furthermore, SB203580 blocked stretch-induced NF-kappaB activation during myogenesis, not through down-regulation of degradation of IkappaB-alpha, and consequent translocation of the p65 subunit of NF-kappaB to the nucleus. It is likely that stretch-induced NF-kappaB activation by phosphorylation of p65 NF-kappaB. Moreover, depletion of p38alpha using siRNA significantly reduces stretch-induced phosphorylation of RelA and NF-kappaB activity. These results provides the first evidence of a cross-talk between p38 MAPK and NF-kappaB signaling pathways during stretch-induced myogenesis, with phosphorylation of RelA being one of the effectors of this promyogenic mechanism. The alpha isoform of p38MAP kinase regulates the transcriptional activation of NF-kappaB following stimulation with cyclic stretch.
Ji
Guoping
G
Department of Orthodontics, College of Stomatology, Ninth People's Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Research Institute of Stomatology, Shanghai 200011, China.
Liu
Dongxu
D
Liu
Jing
J
Gao
Hui
H
Yuan
Xiao
X
Shen
Gang
G
D000818:Animals; D002460:Cell Line; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007093:Imidazoles / Q000494:pharmacology; D040542:Mechanotransduction, Cellular / Q000235:genetics; D051379:Mice; D024510:Muscle Development / Q000187:drug effects / Q000235:genetics* / Q000502:physiology; D032446:Myoblasts / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D010766:Phosphorylation; D011725:Pyridines / Q000494:pharmacology; D013718:Tensile Strength; D051996:Transcription Factor RelA / Q000378:metabolism*; D015533:Transcriptional Activation; D015854:Up-Regulation; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
D004791:Enzyme Inhibitors; D007093:Imidazoles; D011725:Pyridines; D051996:Transcription Factor RelA; D048051:p38 Mitogen-Activated Protein Kinases; C093642:SB 203580