Abstract
The Ca^2+^‐modulated protein of the EF‐hand type, S100B, was shown to inhibit rat L6 myoblast differentiation and myotube formation by interacting with a high affinity with an unidentified receptor (Sorci et al., 2003). We show here that S100B independently inhibits the MKK6‐p38 MAPK pathway and stimulates the Ras‐MEK‐ERK1/2 pathway. The inhibitory effect of S100B on p38 MAPK translates into a defective induction of the muscle‐specific transcription factor myogenin and the antiproliferative factor p21^WAF1^, while S100B's stimulatory effect on ERK1/2 results in stimulation of myoblast proliferation via cyclin D1 induction and Rb phosphorylation and protection against apoptosis via activation of NF‐κB transcriptional activity. Also, the S100B's effects that are mediated by the Ras‐MEK‐ERK1/2 pathway that is, stimulation of proliferation and protection against apoptosis, depend on reactive oxygen species production, being inhibited by antioxidants, while the S100B inhibitory effect on the MKK6‐p38 MAPK pathway is not. We propose that S100B might participate in the regulation of myoblast differentiation by stimulating myoblast proliferation, protecting myoblasts against apoptosis, and modulating myotube formation. J. Cell. Physiol. 207: 461–470, 2006. © 2006 Wiley‐Liss, Inc.