Fc Epsilon RI Signaling

Fc ε RI belongs to the immunoglobulin superfamily. It plays a role in controlling allergic responses in mast cells, eosinophils and basophils. Fc ε RI is a multimeric receptor consisting of an α chain that is required for binding of the IgE molecule and β and γ chains involved in signal transduction. Interaction of FcεRI bound IgE with a multivalent antigen, crosslinks FcεRI on the cell surface leading to intiation of signal transduction.Activation of Fc ε RI results in the phosphorylation of immunoreceptor tyrosine-based activation motif (ITAM) regions in its β and γ subunits by Lyn kinase. This is followed by the activation of SYK which is central to the activation of several adapter proteins like LAT, SPL-76, SOS and GRB2. Adapter proteins now allow for the assembly and activation of several downstream signaling pathways: 1) PLC γ activation results in increased intracellular Ca+2 as well as PKC activation, both events are crucial for degranultion and histamine release in mast cells. 2) Activation of Vav leads to activation of the Ras/Raf/MEK/ERk pathway which results in production of eicosanoids and cytokines. Vav also activates Rac which activates JNK and p38MaPk both resulting in cytokine induction. These mediators contribute to development of the acute and chronic symptoms of allergic reactions such as erythema, pruritis, bronchiolar constriction and shock.