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The Nedd4-2/Ndfip1 axis is a negative regulator of IgE-mediated mast cell activation.
Yip, Kwok Ho; Kolesnikoff, Natasha; Hauschild, Nicholas; Biggs, Lisa; Lopez, Angel F; Galli, Stephen J; Kumar, Sharad; Grimbaldeston, Michele A.
Afiliación
  • Yip KH; Centre for Cancer Biology, University of South Australia and SA Pathology, Adelaide, South Australia 5000, Australia.
  • Kolesnikoff N; Centre for Cancer Biology, University of South Australia and SA Pathology, Adelaide, South Australia 5000, Australia.
  • Hauschild N; Centre for Cancer Biology, University of South Australia and SA Pathology, Adelaide, South Australia 5000, Australia.
  • Biggs L; Centre for Cancer Biology, University of South Australia and SA Pathology, Adelaide, South Australia 5000, Australia.
  • Lopez AF; Centre for Cancer Biology, University of South Australia and SA Pathology, Adelaide, South Australia 5000, Australia.
  • Galli SJ; School of Medicine, University of Adelaide, Adelaide, South Australia 5005, Australia.
  • Kumar S; Departments of Pathology and of Microbiology and Immunology, and the Sean N. Parker Center for Allergy and Asthma Research, Stanford University School of Medicine, Stanford, California 94305-5176, USA.
  • Grimbaldeston MA; Centre for Cancer Biology, University of South Australia and SA Pathology, Adelaide, South Australia 5000, Australia.
Nat Commun ; 7: 13198, 2016 10 27.
Article en En | MEDLINE | ID: mdl-27786273
Cross-linkage of the high-affinity immunoglobulin E (IgE) receptor (FcɛRI) on mast cells by antigen ligation has a critical role in the pathology of IgE-dependent allergic disorders, such as anaphylaxis and asthma. Restraint of intracellular signal transduction pathways that promote release of mast cell-derived pro-inflammatory mediators is necessary to dampen activation and restore homoeostasis. Here we show that the ligase Nedd4-2 and the adaptor Ndfip1 (Nedd4 family interacting protein 1) limit the intensity and duration of IgE-FcɛRI-induced positive signal transduction by ubiquitinating phosphorylated Syk, a tyrosine kinase that is indispensable for downstream FcɛRI signalosome activity. Importantly, loss of Nedd4-2 or Ndfip1 in mast cells results in exacerbated and prolonged IgE-mediated cutaneous anaphylaxis in vivo. Our findings reveal an important negative regulatory function for Nedd4-2 and Ndfip1 in IgE-dependent mast cell activity.
Asunto(s)

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Inmunoglobulina E / Proteínas Portadoras / Ubiquitina-Proteína Ligasas Nedd4 / Mastocitos / Proteínas de la Membrana Límite: Animals Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2016 Tipo del documento: Article País de afiliación: Australia

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Inmunoglobulina E / Proteínas Portadoras / Ubiquitina-Proteína Ligasas Nedd4 / Mastocitos / Proteínas de la Membrana Límite: Animals Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2016 Tipo del documento: Article País de afiliación: Australia
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