| First Author | López-Peláez M | Year | 2011 |
| Journal | Eur J Immunol | Volume | 41 |
| Issue | 6 | Pages | 1733-41 |
| PubMed ID | 21469113 | Mgi Jnum | J:176489 |
| Mgi Id | MGI:5291906 | Doi | 10.1002/eji.201041101 |
| Citation | Lopez-Pelaez M, et al. (2011) Cot/tpl2 activity is required for TLR-induced activation of the Akt p70 S6k pathway in macrophages: Implications for NO synthase 2 expression. Eur J Immunol 41(6):1733-41 |
| abstractText | LPS stimulation activates IKK and different MAP kinase pathways, as well as the PI3K-Akt-mTOR-p70 S6k pathway, a negative regulator of these MyD88-dependent intracellular signals. Here, we show that Cot/tpl2, a MAP3K responsible for the activation of the MKK1-Erk1/2, controls P-Ser473 Akt and P-Thr389 p70 S6k phosphorylation in LPS-stimulated macrophages. Analysis of the intracellular signalling in Cot/tpl2 KO macrophages versus WT macrophages reveals lower IkappaBalpha recovery and higher phosphorylation of JNK and p38alpha after 1 h of LPS stimulation. Moreover, Cot/tpl2 deficiency increases LPS-induced NO synthase 2 (NOS2) expression in macrophages. Inhibition of the PI3K pathway abolishes the differences in IkappaBalpha and NOS2 expression between Cot/tpl2 KO and WT macrophages following LPS administration. Furthermore, in zymosan- and polyI:C-stimulated macrophages, Cot/tpl2 mediates P-Ser473 Akt phosphorylation, increases IkappaBalpha levels and decreases NOS2 expression. In conclusion, these data reveal a novel role for the Cot/tpl2 pathway in mediating TLR activation of the Akt-mTOR-p70 S6k pathway, allowing Cot/tpl2 to fine-control the activation state of other signalling pathways. |
