PXD035076-1

PXD035076 is an original dataset announced via ProteomeXchange.

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

Revision	Datetime	Status	ChangeLog Entry
0	2022-07-04 14:52:56	ID requested
⏵ 1	2022-07-22 04:17:22	announced

Dataset with its publication pending

submitter keyword: Insulin receptor,phenylalanylation,Type 2 diabetes

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

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PRIDE project URI

• PRIDE
  1. PXD035076
     1. Label: PRIDE project
     2. Name: Phenylalanine Impairs Insulin Signaling and Inhibits Glucose Uptake Through Modification of IRβ