LAT Is Essential for FcεRI-Mediated Mast Cell Activation

Mast Cells Produce Interleukin-25 upon FcεRI-mediated Activation

Interleukin (IL)-25 is a recently described T helper 2 (Th2) cell-derived cytokine that belongs to IL-17 family and induces the production of IL-4, IL-5, and IL-13 from an unidentified non-T cell population. Here, we show that mast cells are also potent IL-25-producing cells. When bone marrow-derived mast cells (BMMCs) were stimulated by IgE cross-linking, IL-25 mRNA was induced within 30 min i...

The Four Distal Tyrosines Are Required for LAT-dependent Signaling in FcɛRI-mediated Mast Cell Activation

The linker for activation of T cells (LAT) is an adaptor protein critical for Fc epsilon RI-mediated mast cell activation. LAT is a substrate of the tyrosine kinases activated after TCR and Fc epsilon RI engagement. After phosphorylation of the cytosolic domain of LAT, multiple signaling molecules such as phospholipase C-gamma1, Grb2, and Gads associate with phosphorylated LAT via their SH2 dom...

Rcan1 negatively regulates FcεRI-mediated signaling and mast cell function

Aggregation of the high affinity IgE receptor (Fc epsilonRI) activates a cascade of signaling events leading to mast cell activation. Subsequently, inhibitory signals are engaged for turning off activating signals. We identified that regulator of calcineurin (Rcan) 1 serves as a negative regulator for turning off Fc epsilonRI-mediated mast cell activation. Fc epsilonRI-induced Rcan1 expression ...

High resolution mapping of mast cell membranes reveals primary and secondary domains of FcεRI and LAT

In mast cells, cross-linking the high-affinity IgE receptor (Fc(epsilon)RI) initiates the Lyn-mediated phosphorylation of receptor ITAMs, forming phospho-ITAM binding sites for Syk. Previous immunogold labeling of membrane sheets showed that resting Fc(epsilon)RI colocalize loosely with Lyn, whereas cross-linked Fc(epsilon)RI redistribute into specialized domains (osmiophilic patches) that excl...

Zinc Is Required for Fc RI-Mediated Mast Cell Activation