Abstract

Mast cells elicit allergic responses through degranulation and release of proinflammatory mediators after antigen crosslinking of the immunoglobulin E receptor Fc|[epsi]|RI. Proteins of the 'regulator of G protein signaling' (RGS) family negatively control signaling mediated by G protein–coupled receptors through GTPase-accelerating protein activity. Here we show that RGS13 inhibited allergic responses by physically interacting with the regulatory p85α subunit of phosphatidylinositol-3-OH kinase in mast cells and disrupting its association with an Fc|[epsi]|RI-activated scaffolding complex. Rgs13|[minus]|/|[minus]| mice had enhanced immunoglobulin E–mediated mast cell degranulation and anaphylaxis. Thus, RGS13 inhibits the assembly of immune receptor–induced signalosomes in mast cells. Abnormal RGS13 expression or function may contribute to disorders of amplified mast cell activity, such as idiopathic anaphylaxis.