Skip to main content
. Author manuscript; available in PMC: 2010 Feb 1.
Published in final edited form as: Nat Rev Immunol. 2008 Dec;8(12):923. doi: 10.1038/nri2449

Figure 4. The mammalian target of rapamycin pathway, amino-acid sensing and inflammation.

Figure 4

Mammalian target of rapamycin (mTOR) is an important checkpoint kinase that transmits signals related to amino-acid sufficiency and protein synthesis. A hyperactive mTOR pathway has been associated with increased signalling induced by the unfolded-protein response (UPR) and with the activation of JUN N-terminal kinase (JNK), which can lead to increased inflammation and insulin resistance through serine phosphorylation of insulin receptor substrate 1 (IRS1). Inflammation can further activate mTOR, through IκB kinase (IKK)-mediated phosphorylation of tuberous sclerosis complex 1 (TSC1), as can the UPR through the induction of activating transcription factor 6 (ATF6; not shown). This leads to a vicious inflammatory cycle in metabolically stressed cells. The UPR and IKK activation can also lead to leptin resistance through the induction of polypyrimidine tract-binding protein 1β (PTB1β) and suppressor of cytokine signalling 3 (SOCS3), respectively. 4EBP1, eukaryotic translation-initiation factor 4E-binding protein 1; GβL, G-protein β-subunit-like protein; IκB, inhibitor of nuclear factor-κB; mTORC2, mTOR complex 2; RAPTOR, regulatory associated protein of mTOR; RHEB, RAS homology enriched in brain; S6K1, ribosomal protein S6 kinase 1; TNF, tumour-necrosis factor.