Integrin signaling in neutrophils and macrophages uses adaptors containing immunoreceptor tyrosine-based activation motifs
Integrin signaling in neutrophils and macrophages uses adaptors containing immunoreceptor tyrosine-based activation motifs
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DOI：
10.1038/ni1407
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发表时间：
2006-12-01
影响因子：
30.5
通讯作者：
Lowell, Clifford A.
中科院分区：
文献类型：
--
作者：
Mocsai, Attila;Abram, Clare L.;Lowell, Clifford A.
在炎症部位，白细胞整联蛋白的连接对于宿主防御所需的细胞效应子功能的激活至关重要。然而，连接整合素连接细胞反应的信号通路知之甚少。在这里，我们表明，在中性粒细胞和巨噬细胞中的整合素信号需要含有免疫受体酪氨酸激活基序（ITAMs）的衔接子。中性粒细胞和巨噬细胞缺乏两个含ITAM的衔接蛋白，DAP 12和FcR γ，是有缺陷的整合素介导的反应。酪氨酸激酶Syk被整联蛋白激活需要DAP 12和FcR γ首先被Src家族激酶磷酸化。中性粒细胞和巨噬细胞与野生型和突变体Syk或DAP 12的逆转录病毒转导证明，Syk的Src同源2结构域和DAP 12的ITAM是整合素信号传导所需的。我们的数据表明，整合素信号激活细胞反应的中性粒细胞和巨噬细胞的收益的免疫受体样机制。
At sites of inflammation, ligation of leukocyte integrins is critical for the activation of cellular effector functions required for host defense. However, the signaling pathways linking integrin ligation to cellular responses are poorly understood. Here we show that integrin signaling in neutrophils and macrophages requires adaptors containing immunoreceptor tyrosine-based activation motifs (ITAMs). Neutrophils and macrophages lacking two ITAM-containing adaptor proteins, DAP12 and FcR gamma, were defective in integrin-mediated responses. Activation of the tyrosine kinase Syk by integrins required that DAP12 and FcRy were first phosphorylated by Src family kinases. Retroviral transduction of neutrophils and macrophages with wild-type and mutant Syk or DAP12 demonstrated that the Src homology 2 domains of Syk and the ITAM of DAP12 were required for integrin signaling. Our data show that integrin signaling for the activation of cellular responses in neutrophils and macrophages proceeds by an immunoreceptor-like mechanism.