Dataset Information

Glutamyl-prolyl-tRNA synthetase 1 coordinates early endosomal anti-inflammatory AKT signaling

ABSTRACT: 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

INSTRUMENT(S): Orbitrap Exploris 240

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Cell Culture

SUBMITTER: Ga Seul Lee

LAB HEAD: Myung Hee Kim

PROVIDER: PXD036072 | Pride | 2022-10-12

REPOSITORIES: Pride

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			Action	DRS
	1_noLPS_Vehicle_Gel01.raw	Raw
	1_noLPS_Vehicle_Gel02.raw	Raw
	1_noLPS_Vehicle_Gel03.raw	Raw
	1_noLPS_Vehicle_Gel04.raw	Raw
	1_noLPS_Vehicle_Gel05.raw	Raw

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Glutamyl-prolyl-tRNA synthetase 1 coordinates early endosomal anti-inflammatory AKT signaling.

Lee Eun-Young EY Kim Su-Man SM Hwang Jung Hwan JH Jang Song Yee SY Park Shinhye S Choi Sanghyeon S Lee Ga Seul GS Hwang Jungwon J Moon Jeong Hee JH Fox Paul L PL Kim Sunghoon S Lee Chul-Ho CH Kim Myung Hee MH

Nature communications 20221029 1

The 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 phosphorylates Ser999 of EPRS1 in the cytoplasmic multi-tRNA synthetase complex, inducing release of EPRS1. EPRS1 compartmentalizes AKT to early endos ...[more]

PMID: 36309524

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