kine production (IL-6 and IL-13) with no affect on degranulation. This finding was associated with a reduction in the tyrosine phosphorylation of SHIP-1, a negative regulator of signaling. Y225 plays a crucial role in the interaction between the FcεRIβ chain and SHIP-1 following FcεRI stimulation. Thus, the FcεRIβ chain ITAM may mediate negative signals affecting mast cell responses.

Further studies have demonstrated that the strength of FcεRI engagement determines whether the FcεRIβ chain functions as a positive or negative regulator (Figure [5](#F5){ref-type="fig"}). Upon exposure to low-intensity stimuli, the Lyn-dependent amplifying signals through FcεRIβ can mediate weak positive signals but are insufficient to induce negative signals including SHIP-1; meanwhile, upon exposure to high-intensity stimuli, the FcεRIβ chain increases Lyn-dependent signals considerably, robustly activating both the positive and negative signals simultaneously. Consequently, the FcεRIβ chain increases degranulation and cytokine production in the presence of low-intensity stimuli, whereas it decreases degranulation and cytokine production in the presence of high-intensity stimuli (Nunomura et al., [@B35]; Xiao et al., [@B48]).

![**Positive and negative regulation of FcεRI-dependent mast cell activation by the FcεRIβ ITAM**. Y→F β (αβ~FFF~γ2) mast cells exhibit reduced degranulation and cytokine production following exposure to a "low-intensity" stimulus (left dashed line), whereas the cells exhibit increased degranulation and cytokine production following exposure to a "high-intensity" stimulus (right dashed line). The FcεRI stimulation that induces the optimal degranulation response of wild-type (αβ~YYY~γ2) mast cells (middle dashed line) triggered a normal degranulation response but increased cytokine production in αβ~FFF~γ2 mast cells.](fimmu-03-00112-g005){#F5}

Hck and phospholipase C β3 (PLCβ3) are reportedly involved in regulation of mast cell functions by the FcεRIβ chain and Lyn (Hong et