| Accession |
PRJCA027541 |
| Title |
Methylene-bridge tryptophan fatty acylation regulates PI3K-AKT signaling and glucose uptake |
| Relevance |
Medical |
| Data types |
Raw sequence reads
Proteome
|
| Organisms |
Mus musculus
|
| Description |
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 δ1 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. |
| Sample scope |
Monoisolate |
| Release date |
2024-06-29 |
| Publication |
| PubMed ID |
Article title |
Journal name |
DOI |
Year |
| 35294873
|
|
|
|
|
|
|
| Grants |
| Agency |
program |
Grant ID |
Grant title |
| Ministry of Science and Technology of the People's Republic of China (MOST)
|
|
2018YFA0800300
|
|
| Ministry of Science and Technology of the People's Republic of China (MOST)
|
|
2018YFA0801300
|
|
| National Natural Science Foundation of China (NSFC)
|
|
31821002
|
|
|
|
| Submitter |
Haowen
Yu (19110700004@fudan.edu.cn)
|
| Organization |
Fudan University |
| Submission date |
2024-06-29 |
