Mast cell environment regulates PI3Kγ activation.

<p>Coincident with migration and adhesion of mast cells, adaptor protein p84 relays the GPCR signal from GPCR-mediated dissociation of trimeric G proteins to activate the PI3Kγ complex. However, when mast cells degranulate, FcεRI receptors are clustered via IgE/antigen complexes, and a signaling cascade triggers intracellular Ca²⁺ store depletion and the opening of store-operated Ca²⁺ channels. The resulting increase in calcium ion concentration and PLCγ-derived diacylglycerol activates PKCβ, which binds to p110γ and subsequently phosphorylates Ser582. This phosphorylated p110γ can no longer interact with p84, and the PI3Kγ complex is therefore unresponsive to GPCR inputs.