[en] 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.
Disciplines :
Biochemistry, biophysics & molecular biology
Author, co-author :
Zbinden-Foncea, Hermann
Deldicque, Louise
Pierre, Nicolas ; Université de Liège - ULiège > Département des sciences cliniques > Hépato-gastroentérologie
Francaux, Marc
Raymackers, Jean-Marc
Language :
English
Title :
TLR2 and TLR4 activation induces p38 MAPK-dependent phosphorylation of S6 kinase 1 in C2C12 myotubes.
Publication date :
2012
Journal title :
Cell Biology International
ISSN :
1065-6995
eISSN :
1095-8355
Publisher :
Wiley-Blackwell, New York, United States - New York
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