Suppression of immunoglobulin E-mediated allergic responses by regulator of G protein signaling 13
Suppression of immunoglobulin E-mediated allergic responses by regulator of G protein signaling 13
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DOI：
10.1038/ni1533
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发表时间：
2008-01-01
影响因子：
30.5
通讯作者：
Druey, Kirk M.
中科院分区：
文献类型：
--
作者：
Bansal, Geetanjali;Xie, Zhihui;Druey, Kirk M.
肥大细胞通过免疫球蛋白E受体Fc区RI的抗原交联后的脱粒和促炎介质的释放引起过敏反应。“G蛋白信号传导调节因子”（MISS）家族的蛋白质通过GTP酶加速蛋白活性负性控制由G蛋白偶联受体介导的信号传导。在这里，我们表明，RGS 13抑制过敏反应的物理相互作用与调节p85 α亚基的磷脂酰肌醇-3-OH激酶在肥大细胞和破坏其与Fc β RI激活的支架复合物。Rgs 13（-/-）小鼠免疫球蛋白E介导的肥大细胞脱粒和过敏反应增强。因此，RGS 13抑制肥大细胞中免疫受体诱导的信号体的组装。异常的RGS 13表达或功能可能导致肥大细胞活性增强的病症，例如特发性过敏反应。
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.