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Upon the engagement of FcεRI with IgE and a multivalent antigen, the rapid tyrosyl phosphorylation of the FcεRIβ and γ chain ITAMs is initiated; this, in turn, leads to effector functions, such as degranulation, the *de novo* synthesis of lipid mediators, and cytokine production. The tyrosine phosphorylation of the FcεRIβ chain ITAM occurs through trans-phosphorylation by the src family tyrosine kinase (PTK) Lyn.

Earlier studies found that the FcεRIβ chain acts as an amplifier of FcεRIγ-mediated signaling. The mutation of two canonical tyrosines in the FcεRIβ chain ITAM has been shown to abolish the phosphorylation of both the FcεRIβ and γ chain ITAMs in a rodent mast cell line (Jouvin et al., [@B18]). Similarly, Lyn KO mast cells showed a reduction in the phosphorylation of the FcεRIβ and γ chains (Nishizumi and Yamamoto, [@B33]). Furthermore, in fibroblasts expressing human FcεRI, it was revealed that upon receptor engagement, cells expressing the trimeric form of FcεRI (αγ2) exhibit less Lyn-dependent tyrosine phosphorylation of the FcεRIγ chain ITAM and less subsequent tyrosine phosphorylation of Syk kinase (Lin et al., [@B26]) compared to cells expressing the tetrameric form of FcεRI (αβγ2).

These studies show that the FcεRIβ chain is associated with a fivefold- to sevenfold increase in FcεRI signaling through the FcεRIγ chain ITAM. Researchers have long recognized the classical function of the FcεRIβ chain ITAM as a signal amplifier. However, studies by our group recently revealed novel functions of the FcεRIβ chain ITAM and Lyn in the negative regulation of cell activation and effector functions.

Insights into the Novel Roles of the FcεRIβ Chain in FcεRI Signaling and Mast Cell Activation
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The generation of FcεRIβ chain KO mice (Hiraoka et al., [@B16]) and the development of retroviral gene transfer have contributed greatly to the