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.
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Authors | Yuichi Sekine, Keigo Nishida, Satoru Yamasaki, Ryuta Muromoto, Shigeyuki Kon, Jun-Ichi Kashiwakura, Kodai Saitoh, Sumihito Togi, Akihiko Yoshimura, Kenji Oritani, Tadashi Matsuda |
Journal | Journal of immunology (Baltimore, Md. : 1950)
(J Immunol)
Vol. 192
Issue 8
Pg. 3488-95
(Apr 15 2014)
ISSN: 1550-6606 [Electronic] United States |
PMID | 24616480
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Adaptor Proteins, Signal Transducing
- Cytokines
- Receptors, IgE
- STAP2 protein, mouse
- Immunoglobulin E
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Topics |
- Adaptor Proteins, Signal Transducing
(genetics, metabolism)
- Anaphylaxis
(genetics, immunology, metabolism)
- Animals
- Bone Marrow Cells
(immunology, metabolism)
- Cell Proliferation
- Cytokines
(biosynthesis)
- Disease Models, Animal
- Immunoglobulin E
(immunology)
- Mast Cells
(immunology, metabolism)
- Mice
- Mice, Knockout
- Protein Binding
- Receptors, IgE
(metabolism)
- Signal Transduction
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