Article abstract
Nature Immunology 9, 73 - 80 (2008)
Published online: 18 November 2007 | doi:10.1038/ni1533
Suppression of immunoglobulin E–mediated allergic responses by regulator of G protein signaling 13
Geetanjali Bansal1,3, Zhihui Xie1,3, Sudhir Rao2,4, Karl H Nocka2,4 & Kirk M Druey1
Abstract
Mast cells elicit allergic responses through degranulation and release of proinflammatory mediators after antigen crosslinking of the immunoglobulin E receptor Fc
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 p85
subunit of phosphatidylinositol-3-OH kinase in mast cells and disrupting its association with an FcRI-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.
- Molecular Signal Transduction Section, Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA.
- UCB Pharma, Cambridge, Massachusetts 02139, USA.
- These authors contributed equally to this work.
- Present addresses: Merck Research Laboratories, Boston, Massachusetts 02115, USA (S.R.) and Wyeth Research, Cambridge, Massachusetts 02140, USA (K.H.N).
Correspondence to: Kirk M Druey1 e-mail: kdruey@niaid.nih.gov
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