Raf kinase inhibitor protein negatively regulates FcεRI-mediated mast cell activation and allergic response.

ABSTRACT: The signaling cascades triggered by the cross-linkage of immunoglobulin E (IgE) with its high-affinity receptor (FcεRI) on mast cells contribute to multiple allergic disorders, such as asthma, rhinitis, and atopic dermatitis. Restraint of intracellular signals for mast cell activation is essential to restore homeostasis. In this study, we found that Raf kinase inhibitor protein (RKIP) negatively regulated mast cell activation. RKIP-deficient mast cells showed greater IgE-FcεRI-mediated activation than wild-type mast cells. Consistently, RKIP deficiency in mast cells rendered mice more sensitive to IgE-FcεRI-mediated allergic responses and ovalbumin-induced airway inflammation. Mechanistically, RKIP interacts with the p85 subunit of PI3K, prevents it from binding to GRB2-associated binding

SUBMITTER: Lin W 

PROVIDER: S-EPMC6196501 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature