| First Author | Hamilton KS | Year | 2014 |
| Journal | Sci Signal | Volume | 7 |
| Issue | 329 | Pages | ra55 |
| PubMed ID | 24917592 | Mgi Jnum | J:259187 |
| Mgi Id | MGI:6142423 | Doi | 10.1126/scisignal.2005169 |
| Citation | Hamilton KS, et al. (2014) T cell receptor-dependent activation of mTOR signaling in T cells is mediated by Carma1 and MALT1, but not Bcl10. Sci Signal 7(329):ra55 |
| abstractText | Signaling to the mechanistic target of rapamycin (mTOR) regulates diverse cellular processes, including protein translation, cellular proliferation, metabolism, and autophagy. Most models place Akt upstream of the mTOR complex, mTORC1; however, in T cells, Akt may not be necessary for mTORC1 activation. We found that the adaptor protein Carma1 [caspase recruitment domain (CARD)-containing membrane-associated protein 1] and at least one of its associated proteins, the paracaspase MALT1 (mucosa-associated lymphoid tissue lymphoma translocation protein 1), were required for optimal activation of mTOR in T cells in response to stimulation of the T cell receptor (TCR) and the co-receptor CD28. However, Bcl10, which binds to Carma1 and MALT1 to form a complex that mediates signals from the TCR to the transcription factor NF-kappaB (nuclear factor kappaB), was not required. The catalytic activity of MALT1 was required for the proliferation of stimulated CD4+ T cells, but not for early TCR-dependent activation events. Consistent with an effect on mTOR, MALT1 activity was required for the increased metabolic flux in activated CD4+ T cells. Together, our data suggest that Carma1 and MALT1 play previously unappreciated roles in the activation of mTOR signaling in T cells after engagement of the TCR. |
