biostudies-literatureUnknown14Guo YMRGPRX2, a G-protein-coupled-seven transmembrane domain receptor, is mainly expressed in mast cells and neurons and is involved in skin immunity and pain. It is implicated in the pathophysiology of non-IgE-mediated immediate hypersensitivity and has been related to adverse drug reactions. Moreover, a role has been proposed in asthma, atopic dermatitis, contact dermatitis, and chronic spontaneous urticaria. Although it has a prominent role in disease, its signaling transduction is poorly understood. This study shows that MRGPRX2 activation with substance P increased Lysyl t-RNA synthetase (LysRS) translocation to the nucleus. LysRS is a moonlighting protein with a dual role in protein translation and IgE signaling in mast cells. Upon allergen- IgE-FcεRI crosslinking, LysRS is translocated tFrontiers in immunology1154108https://www.ebi.ac.uk/biostudies/studies/S-EPMC10206166biostudies-literatureMRGPRX2 signaling involves the Lysyl-tRNA synthetase and MITF pathway.PMC10206166Olle LGuo YProano-Perez EGuerrero MMunoz-Cano RMartin MAparicio CfalseMRGPRX2 signaling involves the Lysyl-tRNA synthetase and MITF pathway.MRGPRX2, a G-protein-coupled-seven transmembrane domain receptor, is mainly expressed in mast cells and neurons and is involved in skin immunity and pain. It is implicated in the pathophysiology of non-IgE-mediated immediate hypersensitivity and has been related to adverse drug reactions. Moreover, a role has been proposed in asthma, atopic dermatitis, contact dermatitis, and chronic spontaneous urticaria. Although it has a prominent role in disease, its signaling transduction is poorly understood. This study shows that MRGPRX2 activation with substance P increased Lysyl t-RNA synthetase (LysRS) translocation to the nucleus. LysRS is a moonlighting protein with a dual role in protein translation and IgE signaling in mast cells. Upon allergen- IgE-FcεRI crosslinking, LysRS is translocated t2023-01-01T00:00:00Z20232025-04-19T06:22:10.2Z2025-04-19T06:22:10.2ZS-EPMC102061663723417210.3389/fimmu.2023.1154108