Unknown

Dataset Information

0

The Nedd4-2/Ndfip1 axis is a negative regulator of IgE-mediated mast cell activation.


ABSTRACT: Cross-linkage of the high-affinity immunoglobulin E (IgE) receptor (Fc?RI) 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-Fc?RI-induced positive signal transduction by ubiquitinating phosphorylated Syk, a tyrosine kinase that is indispensable for downstream Fc?RI 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.

SUBMITTER: Yip KH 

PROVIDER: S-EPMC5095291 | biostudies-literature | 2016 Oct

REPOSITORIES: biostudies-literature

altmetric image

Publications

The Nedd4-2/Ndfip1 axis is a negative regulator of IgE-mediated mast cell activation.

Yip Kwok Ho KH   Kolesnikoff Natasha N   Hauschild Nicholas N   Biggs Lisa L   Lopez Angel F AF   Galli Stephen J SJ   Kumar Sharad S   Grimbaldeston Michele A MA  

Nature communications 20161027


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) lim  ...[more]

Similar Datasets

| S-EPMC3179515 | biostudies-literature
| S-EPMC4871253 | biostudies-literature
| S-EPMC4038093 | biostudies-literature
| S-EPMC3594621 | biostudies-literature
| S-EPMC6516833 | biostudies-literature
| S-EPMC3412263 | biostudies-literature
2022-07-05 | GSE206630 | GEO
| S-EPMC5865592 | biostudies-literature
2021-01-12 | GSE164537 | GEO
| S-EPMC6159977 | biostudies-literature