{"id":259,"date":"2025-04-01T00:11:18","date_gmt":"2025-04-01T00:11:18","guid":{"rendered":"https:\/\/bioreg.kyushu-u.ac.jp\/labo\/iden\/wp\/?post_type=service&p=259"},"modified":"2025-07-21T03:30:17","modified_gmt":"2025-07-21T03:30:17","slug":"paper-11","status":"publish","type":"service","link":"https:\/\/bioreg.kyushu-u.ac.jp\/labo\/iden\/publication\/paper-11\/","title":{"rendered":"JACI 2023 (Kunimura et al.)"},"content":{"rendered":"\n

DOCK2 regulates MRGPRX2\/B2-mediated mast cell degranulation and drug-induced anaphylaxis.<\/p>\n\n\n\n

Kunimura K<\/strong>\u2020<\/sup>, Akiyoshi S<\/strong>, Uruno T<\/strong>, Matsubara K<\/strong>, Sakata D<\/strong>, Morino K<\/strong>, Hirotani K<\/strong>, Fukui Y<\/strong> (\u2020<\/sup>corresponding author):<\/p>\n\n\n\n

The Journal of Allergy and Clinical Immunology<\/strong> 151(6): 1415-1420, 2023<\/strong>.<\/p>\n\n\n\n

Background: Drug-induced anaphylaxis is triggered by the direct stimulation of mast cells (MCs) via Mas-related G protein\u2013coupled receptor X2 (MRGPRX2; mouse ortholog MRGPRB2). However, the precise mechanism that links MRGPRX2\/B2 to MC degranulation is poorly understood. Dedicator of cytokinesis 2 (DOCK2) is a Rac activator predominantly expressed in hematopoietic cells. Although DOCK2 regulates migration and activation of leukocytes, its role in MCs remains unknown.
Objective: We aimed to elucidate whether\u2014and if so, how\u2014DOCK2 is involved in MRGPRX2\/B2-mediated MC degranulation and anaphylaxis.
Methods: Induction of drug-induced systemic and cutaneous anaphylaxis was compared between wild-type and DOCK2-deficient mice. In addition, genetic or pharmacologic inactivation of DOCK2 in human and murine MCs was used to reveal its role in MRGPRX2\/B2-mediated signal transduction and degranulation.
Results: Induction of MC degranulation and anaphylaxis by compound 48\/80 and ciprofloxacin was severely attenuated in the absence of DOCK2. Although calcium influx and phosphorylation of several signaling molecules were unaffected, MRGPRB2-mediated Rac activation and phosphorylation of p21-activated kinase 1 (PAK1) were impaired in DOCK2-deficient MCs. Similar results were obtained when mice or MCs were treated with small-molecule inhibitors that bind to the catalytic domain of DOCK2 and inhibit Rac activation.
Conclusion: DOCK2 regulates MRGPRX2\/B2-mediated MC degranulation through Rac activation and PAK1 phosphorylation, thereby indicating that the DOCK2-Rac-PAK1 axis could be a target for preventing drug-induced anaphylaxis.<\/p>\n\n\n\n

https:\/\/researchmap.jp\/-kunimura-\/published_papers\/41119008<\/a><\/p>\n\n\n\n

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