Suppression of immunoglobulin E-mediated allergic responses by regulator of G protein signaling 13.
Mast cells elicit allergic responses through degranulation and release of proinflammatory mediators after antigen crosslinking of the immunoglobulin E receptor FcepsilonRI. 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 p85alpha subunit of phosphatidylinositol-3-OH kinase in mast cells and disrupting its association with an FcepsilonRI-activated scaffolding complex. Rgs13-/- 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.
Bansal
Geetanjali
G
Molecular Signal Transduction Section, Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA.
Xie
Zhihui
Z
Rao
Sudhir
S
Nocka
Karl H
KH
Druey
Kirk M
KM
D000707:Anaphylaxis / Q000276:immunology*; D000818:Animals; D015550:Cell Degranulation; D002478:Cells, Cultured; D004789:Enzyme Activation; D007073:Immunoglobulin E / Q000276:immunology*; D008407:Mast Cells / Q000276:immunology / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D020710:RGS Proteins / Q000235:genetics / Q000276:immunology*; D017455:Receptors, IgE / Q000276:immunology*; D015398:Signal Transduction
D007073:Immunoglobulin E; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D020710:RGS Proteins; D017455:Receptors, IgE