SMG1 and mTOR are PIKK family members associated with cancer. The best characterised role of SMG1 is in the initiation of nonsense mediated decay (NMD). However, a diverse range of poorly described roles have been described in genotoxic stress, oxidative stress, hypoxia, and apoptosis. Although knockout of SMG1 in mice is embryonic lethal, haploinsufficiency leads to abnormal growth, chronic inflammation and cancer. mTOR forms two distinct complexes, mTORC1 and mTORC2, and regulates cell growth and metabolism. SMG1 inhibits growth via mTOR in planarian worms and the phenotype in mice suggests this regulation may be conserved in mammals. Using down regulation of SMG1 followed by treatment with IGF1 or serum to induce signalling from mTORC2 and 1 respectively, downstream reporters of mTORC1 (P-S6KThr389) and mTORC2 (P-AktSer473) were upregulated. Upregulation of mTORC1 is at least partly due to feedback from mTORC2 as P-S6KThr389 upregulation can be partially inhibited by Akt inhibition. Phosphorylation of both can be completely inhibited by the mTOR inhibiter INK128. Phosphorylation of mTOR at Ser2481, a marker of mTORC2 complex stability, increased at both baseline and upon growth factor stimulation after SMG1 knockdown. Additionally over expression of SMG1 and a kinase inactive mutant were able to inhibit mTORC2 signalling. Inhibition of NMD with a small molecule inhibiter, NMDi14, did not mimic SMG1 knockdown suggesting an alternative mechanism of action. mTORC2 components (mTOR, RICTOR and SIN1.1) were co-precipitated with SMG1 indicating complex formation with mTORC2. This may have relevance to the action of SMG1 as a tumor suppressor in B-cell malignancies as an inverse correlation between P-AktSer473 and SMG1 expression was observed in a cohort of B cell lymphoma patients and high expression of SMG1 was associated with poorer survival.