title: Signal-transducing adaptor protein-2 controls the IgE-mediated, mast cell-mediated anaphylactic responses.
abstract: Signal-transducing adaptor protein-2 (STAP-2) is a recently identified adaptor protein that regulates immune and inflammatory responses through interactions with a variety of signaling and transcriptional molecules. In the current study, we clarified the physiological role of STAP-2 in mast cell function, a key mediator of IgE-associated allergic responses. STAP-2 is constitutively expressed in mast cells. STAP-2 deficiency in mast cells greatly enhances FcεRI-mediated signals, resulting in the increased tyrosine phosphorylation of the phospholipase C-γ isoform, calcium mobilization, and degranulation. Of importance, STAP-2-deficient mice challenged with DNP-BSA after passive sensitization with anti-DNP IgE show more severe rectal temperature decrease than do wild-type mice. STAP-2-deficient mice also show increased vascular permeability and more severe cutaneous anaphylaxis after DNP-BSA injection. These regulatory functions performed by STAP-2 indicate that there is an interaction between STAP-2 and FcεRI. In addition, our previous data indicate that STAP-2 binds to the phospholipase C-γ isoform and IκB kinase-β. Therefore, our data described in this article strongly suggest that manipulation of STAP-2 expression in mast cells may control the pathogenesis of allergic diseases and have the potential for treating patients with allergy.
authors.affiliation: Department of Immunology, Graduate School of Pharmaceutical Sciences, Hokkaido University, Sapporo 060-0812, Japan;
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Sekine
authors.forename: Keigo
authors.initials: K
authors.lastname: Nishida
authors.forename: Satoru
authors.initials: S
authors.lastname: Yamasaki
authors.forename: Ryuta
authors.initials: R
authors.lastname: Muromoto
authors.forename: Shigeyuki
authors.initials: S
authors.lastname: Kon
authors.forename: Jun-Ichi
authors.initials: J
authors.lastname: Kashiwakura
authors.forename: Kodai
authors.initials: K
authors.lastname: Saitoh
authors.forename: Sumihito
authors.initials: S
authors.lastname: Togi
authors.forename: Akihiko
authors.initials: A
authors.lastname: Yoshimura
authors.forename: Kenji
authors.initials: K
authors.lastname: Oritani
authors.forename: Tadashi
authors.initials: T
authors.lastname: Matsuda
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D000707:Anaphylaxis / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D000818:Animals; D001854:Bone Marrow Cells / Q000276:immunology / Q000378:metabolism; D049109:Cell Proliferation; D016207:Cytokines / Q000096:biosynthesis; D004195:Disease Models, Animal; D007073:Immunoglobulin E / Q000276:immunology*; D008407:Mast Cells / Q000276:immunology* / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D011485:Protein Binding; D017455:Receptors, IgE / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D016207:Cytokines; D017455:Receptors, IgE; C523144:STAP2 protein, mouse; D007073:Immunoglobulin E