| First Author | Zhao Y | Year | 2019 |
| Journal | Nat Commun | Volume | 10 |
| Issue | 1 | Pages | 1349 |
| PubMed ID | 30902986 | Mgi Jnum | J:273264 |
| Mgi Id | MGI:6286780 | Doi | 10.1038/s41467-019-09283-x |
| Citation | Zhao Y, et al. (2019) Microbial recognition by GEF-H1 controls IKKepsilon mediated activation of IRF5. Nat Commun 10(1):1349 |
| abstractText | During infection, transcription factor interferon regulatory factor 5 (IRF5) is essential for the control of host defense. Here we show that the microtubule-associated guanine nucleotide exchange factor (GEF)-H1, is required for the phosphorylation of IRF5 by microbial muramyl-dipeptides (MDP), the minimal structural motif of peptidoglycan of both Gram-positive and Gram-negative bacteria. Specifically, GEF-H1 functions in a microtubule based recognition system for microbial peptidoglycans that mediates the activation of IKKepsilon which we identify as a new upstream IKKalpha/beta and IRF5 kinase. The deletion of GEF-H1 or dominant-negative variants of GEF-H1 prevent activation of IKKepsilon and phosphorylation of IRF5. The GEF-H1-IKKepsilon-IRF5 signaling axis functions independent of NOD-like receptors and is critically required for the recognition of intracellular peptidoglycans and host defenses against Listeria monocytogenes. |
