| First Author | Zhu L | Year | 2019 |
| Journal | Nat Cell Biol | Volume | 21 |
| Issue | 12 | Pages | 1604-1614 |
| PubMed ID | 31792381 | Mgi Jnum | J:282979 |
| Mgi Id | MGI:6384058 | Doi | 10.1038/s41556-019-0429-8 |
| Citation | Zhu L, et al. (2019) TBKBP1 and TBK1 form a growth factor signalling axis mediating immunosuppression and tumourigenesis. Nat Cell Biol 21(12):1604-1614 |
| abstractText | TANK-binding kinase 1 (TBK1) responds to microbial stimuli and mediates the induction of type I interferon (IFN). Here, we show that TBK1 is also a central mediator of growth factor signalling; this function of TBK1 relies on a specific adaptor-TBK-binding protein 1 (TBKBP1). TBKBP1 recruits TBK1 to protein kinase C-theta (PKCtheta) through a scaffold protein, CARD10. This enables PKCtheta to phosphorylate TBK1 at Ser 716, a crucial step for TBK1 activation by growth factors but not by innate immune stimuli. Although the TBK1-TBKBP1 signalling axis is not required for the induction of type I IFN, it mediates mTORC1 activation and oncogenesis. Conditional deletion of either TBK1 or TBKBP1 in lung epithelial cells inhibits tumourigenesis in a mouse model of lung cancer. In addition to promoting tumour growth, the TBK1-TBKBP1 axis facilitates tumour-mediated immunosuppression through a mechanism that involves induction of the checkpoint molecule PD-L1 and stimulation of glycolysis. These findings suggest a PKCtheta-TBKBP1-TBK1 growth factor signalling axis that mediates both tumour growth and immunosuppression. |
