title: TLR2 and TLR4 activation induces p38 MAPK-dependent phosphorylation of S6 kinase 1 in C2C12 myotubes.
abstract: 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 can bind various extracellular ligands, such as FSL-1, lipopolysaccharide (LPS) and/or palmitic acid (PA). We have investigated the link between PA, TLR2/4 and ribosomal S6 kinase 1 (S6K1) in C2C12 myotubes. Incubation with agonists of either TLR2 or TLR4, and with a high concentration of PA, increased S6K1 phosphorylation. 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 these kinases were probably not involved. By using the SB202190 inhibitor, p38 MAPK (mitogen-activated protein kinase) was found to be a key mediator of PA-induced phosphorylation of S6K1. Downregulation 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. Thus TLR2 and TLR4 agonists can increase the level of S6K1 phosphorylation in a p38 MAPK-dependent way in C2C12 myotubes. As PA induced the same intracellular signalling, a novel atypical pathway for PA is induced at the cellular membrane level and results in a higher phosphorylation state of S6K1.
authors.affiliation: Institute of Neuroscience, Université catholique de Louvain, Louvain-la-Neuve, Belgium.
authors.forename: Hermann
authors.initials: H
authors.lastname: Zbinden-Foncea
authors.forename: Louise
authors.initials: L
authors.lastname: Deldicque
authors.forename: Nicolas
authors.initials: N
authors.lastname: Pierre
authors.forename: Marc
authors.initials: M
authors.lastname: Francaux
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Raymackers
mesh_terms: D000818:Animals; D002460:Cell Line; D015536:Down-Regulation; D051379:Mice; D018485:Muscle Fibers, Skeletal / Q000378:metabolism*; D019308:Palmitic Acid / Q000378:metabolism*; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D038744:Ribosomal Protein S6 Kinases, 90-kDa / Q000378:metabolism*; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism; D051195:Toll-Like Receptor 2 / Q000235:genetics / Q000378:metabolism*; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000378:metabolism*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
chemical_list: D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D019308:Palmitic Acid; D051057:Proto-Oncogene Proteins c-akt; D038744:Ribosomal Protein S6 Kinases, 90-kDa; C512964:Rps6ka1 protein, mouse; D058570:TOR Serine-Threonine Kinases; D048051:p38 Mitogen-Activated Protein Kinases