PXD036072

PXD036072 is an original dataset announced via ProteomeXchange.

Title	Glutamyl-prolyl-tRNA synthetase 1 coordinates early endosomal anti-inflammatory AKT signaling
Description	AKT signaling pathway plays critical roles in the resolution of inflammation. However, the underlying mechanisms of anti-inflammatory regulation and signal coordination remain unclear. Here, we report that anti-inflammatory AKT signaling is coordinated by glutamyl-prolyl-tRNA synthetase 1 (EPRS1). Upon inflammatory activation, AKT specifically phosphorylated Ser999 of EPRS1 in the cytoplasmic multi-tRNA synthetase complex, inducing release of EPRS1. The EPRS1 compartmentalized AKT to early endosomes via selective binding to the endosomal membrane lipid phosphatidylinositol 3-phosphate and assembled an AKT signaling complex specific for anti-inflammatory activity. These events promoted AKT activation-mediated GSK3β phosphorylation, which increased anti-inflammatory cytokine production. EPRS1-deficient macrophages could not assemble the early endosomal complex and consequently exacerbated inflammation, decreasing the survival of EPRS1-deficient mice undergoing septic shock and ulcerative colitis. Collectively, our findings show that the housekeeping protein EPRS1 acts as a mediator of inflammatory homeostasis by coordinating compartment-specific AKT signaling
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_08:00:33.141.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Ga Seul Lee
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	methylthiolated residue; acetylated residue; monohydroxylated residue
Instrument	Orbitrap Exploris 240

Revision	Datetime	Status	ChangeLog Entry
0	2022-08-16 05:26:54	ID requested
1	2022-10-12 09:23:16	announced
⏵ 2	2023-11-14 08:00:36	announced	2023-11-14: Updated project metadata.

Lee EY, Kim SM, Hwang JH, Jang SY, Park S, Choi S, Lee GS, Hwang J, Moon JH, Fox PL, Kim S, Lee CH, Kim MH, Glutamyl-prolyl-tRNA synthetase 1 coordinates early endosomal anti-inflammatory AKT signaling. Nat Commun, 13(1):6455(2022) [pubmed]

submitter keyword: Aminoacyl-tRNA Synthetase, Glutamyl-prolyl-tRNA Synthetase 1, Phosphatidylinositol 3-phosphate, PI3K/AKT Signaling Pathway,Multi-tRNA Synthetase Complex, Inflammation, Anti-inflammatory Signaling Complex, Early Endosome

Myung Hee Kim
contact affiliation	Microbiome Convergence Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon 34141, Korea
contact email	mhk8n@kribb.re.kr
lab head
Ga Seul Lee
contact affiliation	Korea Research Institute of Bioscience & Biotechnology (KRIBB)
contact email	rktmf1013@kribb.re.kr
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD036072
     1. Label: PRIDE project
     2. Name: Glutamyl-prolyl-tRNA synthetase 1 coordinates early endosomal anti-inflammatory AKT signaling