Suppression of immunoglobulin E-mediated allergic responses by regulator of G protein signaling 13

Nat Immunol. 2008 Jan;9(1):73-80. doi: 10.1038/ni1533. Epub 2007 Nov 18.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anaphylaxis / immunology*
  • Animals
  • Cell Degranulation
  • Cells, Cultured
  • Enzyme Activation
  • Immunoglobulin E / immunology*
  • Mast Cells / immunology
  • Mast Cells / physiology
  • Mice
  • Mice, Knockout
  • Phosphatidylinositol 3-Kinases / metabolism
  • Phosphoinositide-3 Kinase Inhibitors
  • RGS Proteins / genetics
  • RGS Proteins / immunology*
  • Receptors, IgE / immunology*
  • Signal Transduction


  • Phosphoinositide-3 Kinase Inhibitors
  • RGS Proteins
  • Receptors, IgE
  • Immunoglobulin E

Associated data

  • PDB/AAB84000
  • PDB/CAG46740