| First Author | Hu SH | Year | 2022 |
| Journal | Cell Rep | Volume | 38 |
| Issue | 11 | Pages | 110509 |
| PubMed ID | 35294873 | Mgi Jnum | J:324905 |
| Mgi Id | MGI:7281977 | Doi | 10.1016/j.celrep.2022.110509 |
| Citation | Hu SH, et al. (2022) Methylene-bridge tryptophan fatty acylation regulates PI3K-AKT signaling and glucose uptake. Cell Rep 38(11):110509 |
| abstractText | Protein fatty acylation regulates numerous cell signaling pathways. Polyunsaturated fatty acids (PUFAs) exert a plethora of physiological effects, including cell signaling regulation, with underlying mechanisms to be fully understood. Herein, we report that docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) regulate PI3K-AKT signaling by modifying PDK1 and AKT2. DHA-administered mice exhibit altered phosphorylation of proteins in signaling pathways. Methylene bridge-containing DHA/EPA acylate delta1 carbon of tryptophan 448/543 in PDK1 and tryptophan 414 in AKT2 via free radical pathway, recruit both the proteins to the cytoplasmic membrane, and activate PI3K signaling and glucose uptake in a tryptophan acylation-dependent but insulin-independent manner in cultured cells and in mice. DHA/EPA deplete cytosolic PDK1 and AKT2 and induce insulin resistance. Akt2 knockout in mice abrogates DHA/EPA-induced PI3K-AKT signaling. Our results identify PUFA's methylene bridge tryptophan acylation, a protein fatty acylation that regulates cell signaling and may underlie multifaceted effects of methylene-bridge-containing PUFAs. |
