PXD035076 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | Phenylalanine Impairs Insulin Signaling and Inhibits Glucose Uptake Through Modification of IRβ |
Description | Whether amino acids act on cellular insulin signaling remains unclear, given that increased circulating amino acid levels are associated with the onset of type 2 diabetes (T2D). Here, we report that phenylalanine modifies insulin receptor beta (IRβ) and inactivates insulin signaling and glucose uptake. Mice fed phenylalanine-rich chow or phenylalanine-producing aspartame or overexpressing human phenylalanyl-tRNA synthetase (hFARS) developed insulin resistance and T2D symptoms. Mechanistically, FARS phenylalanylated lysine 1057/1079 of IRβ (F-K1057/1079), inactivating IRβ and preventing insulin from promoting glucose uptake by cells. SIRT1 reversed F-K1057/1079 and counteracted the insulin-inactivating effects of hFARS and phenylalanine. F-K1057/1079 and SIRT1 levels in white blood cells from T2D patients wereare positively and negatively correlated with T2D onset, respectively. Blocking F-K1057/1079 with phenylalaninol sensitizeds insulin signaling and relieveds T2D symptoms in hFARS-transgenic and db/db mice. These findings shed light on the activation of insulin signaling and T2D progression through inhibition of phenylalanylation. |
HostingRepository | PRIDE |
AnnounceDate | 2022-07-22 |
AnnouncementXML | Submission_2022-07-22_04:17:22.366.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | Qian Zhou |
SpeciesList | scientific name: Homo sapiens (Human); NCBI TaxID: 9606; |
ModificationList | modified L-phenylalanine residue |
Instrument | Orbitrap Fusion Lumos |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2022-07-04 14:52:56 | ID requested | |
⏵ 1 | 2022-07-22 04:17:22 | announced | |
Publication List
Dataset with its publication pending |
Keyword List
submitter keyword: Insulin receptor,phenylalanylation,Type 2 diabetes |
Contact List
Shi-Min Zhao |
contact affiliation | Obstetrics & Gynecology Institute, Institute of Metabolism and Integrative Biology, Institutes of Biomedical Sciences, Fudan University, Shanghai, China |
contact email | zhaosm@fudan.edu.cn |
lab head | |
Qian Zhou |
contact affiliation | 86-13162869989 |
contact email | 953975702@qq.com |
dataset submitter | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD035076
- Label: PRIDE project
- Name: Phenylalanine Impairs Insulin Signaling and Inhibits Glucose Uptake Through Modification of IRβ