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-kappa B in response to mechanical Stimulation of myoblasts. Furthermore, SB203580 blocked stretch-induced NF-kappa B activation during myogenesis, not through down-regulation of degradation of I kappa B-alpha, and consequent translocation of the p65 subunit of NF-kappa B to the nucleus It is likely that stretch-induced NF-kappa B activation by phosphorylation of p65 NF-kappa B Moreover, depletion of p38 alpha using siRNA significantly reduces stretch-induced phosphorylation of RelA and NF-kappa B activity These results provides the first evidence of a cross-talk between p38 MAPK and NF-kappa B 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-kappa B following stimulation with cyclic stretch (C) 2009 Elsevier Inc All rights reserved