TLR2 and TLR4 activation induces p38 MAPK-dependent phosphorylation of S6 kinase 1 in C2C12 myotubes.
(2012) Cell Biology International — Vol. 36, n° 12, p. 1107-1113 (2012)
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- Toll-like receptors 2 (TLR2) and 4 (TLR4) are present in the plasma membrane of skeletal muscle cells where their functions remain incompletely resolved. They are able to bind various extra-cellular ligands, such as FSL-1, lipopolysaccharide (LPS) and/or palmitic acid (PA). The purpose of this study was to investigate the link between PA, TLR2/4, and ribosomal S6 kinase 1 (S6K1) in C2C12 myotubes. Incubation with agonists of either TLR2 or TLR4, as well as incubation with high concentration of PA, led to an increase in S6K1 phosphorylation level. Canonical upstream kinases of S6K1, protein kinase B (PKB) and mammalian target of rapamycin complex 1 (mTORC1), were regulated in the opposite way by PA, indicating that those kinases were probably not involved. By using the SB202190 inhibitor, we evidenced that p38 MAPK was a key mediator of PA-induced phosphorylation of S6K1. Down-regulation of either tlr2 or tlr4 gene expression by small interfering RNAs prevented the activation of both p38 MAPK and S6K1 by FSL-1, LPS or PA. In summary, our results showed that TLR2 and TLR4 agonists are able to increase the level of S6K1 phosphorylation in a p38 MAPK dependent way in C2C12 myotubes. As PA induced the same intracellular signaling, we evidenced for the first time an atypical pathway for PA that is induced at the cellular membrane level and results in a higher phosphorylation state of S6K1.
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Zbinden Foncea, H. P., Deldicque, L., Pierre, N., Francaux, M., & Raymackers, J.-M. (2012). TLR2 and TLR4 activation induces p38 MAPK-dependent phosphorylation of S6 kinase 1 in C2C12 myotubes. Cell Biology International, 36(12), 1107-1113. https://doi.org/10.1042/CBI20120081 (Original work published 2012)