| First Author | Najibi M | Year | 2016 |
| Journal | Cell Rep | Volume | 15 |
| Issue | 8 | Pages | 1728-42 |
| PubMed ID | 27184844 | Mgi Jnum | J:233673 |
| Mgi Id | MGI:5787845 | Doi | 10.1016/j.celrep.2016.04.052 |
| Citation | Najibi M, et al. (2016) An Evolutionarily Conserved PLC-PKD-TFEB Pathway for Host Defense. Cell Rep 15(8):1728-42 |
| abstractText | The mechanisms that tightly control the transcription of host defense genes have not been fully elucidated. We previously identified TFEB as a transcription factor important for host defense, but the mechanisms that regulate TFEB during infection remained unknown. Here, we used C. elegans to discover a pathway that activates TFEB during infection. Gene dkf-1, which encodes a homolog of protein kinase D (PKD), was required for TFEB activation in nematodes infected with Staphylococcus aureus. Conversely, pharmacological activation of PKD was sufficient to activate TFEB. Furthermore, phospholipase C (PLC) gene plc-1 was also required for TFEB activation, downstream of Galphaq homolog egl-30 and upstream of dkf-1. Using reverse and chemical genetics, we discovered a similar PLC-PKD-TFEB axis in Salmonella-infected mouse macrophages. In addition, PKCalpha was required in macrophages. These observations reveal a previously unknown host defense signaling pathway, which has been conserved across one billion years of evolution. |
