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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 Cisoform, 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 Cisoform 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.
AuthorsYuichi Sekine, Keigo Nishida, Satoru Yamasaki, Ryuta Muromoto, Shigeyuki Kon, Jun-Ichi Kashiwakura, Kodai Saitoh, Sumihito Togi, Akihiko Yoshimura, Kenji Oritani, Tadashi Matsuda
JournalJournal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 192 Issue 8 Pg. 3488-95 (Apr 15 2014) ISSN: 1550-6606 [Electronic] United States
PMID24616480 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Adaptor Proteins, Signal Transducing
  • Cytokines
  • Receptors, IgE
  • STAP2 protein, mouse
  • Immunoglobulin E
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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