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

被引:55
作者
Bansal, Geetanjali [1 ]
Xie, Zhihui [1 ]
Ra, Sudhir [2 ]
Nocka, Karl H. [2 ]
Druey, Kirk M. [1 ]
机构
[1] NIH, NIAID, Lab Allerg Dis, Mol Signal Transduct Sect, Bethesda, MD 20892 USA
[2] UCB Pharma, Cambridge, MA 02139 USA
关键词
D O I
10.1038/ni1533
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Mast cells elicit allergic responses through degranulation and release of proinflammatory mediators after antigen crosslinking of the immunoglobulin E receptor Fc epsilon RI. Proteins of the 'regulator of G protein signaling' MISS) 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 alpha subunit of phosphatidylinositol-3-OH kinase in mast cells and disrupting its association with an Fc epsilon RI-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.
引用
收藏
页码:73 / 80
页数:8
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