Leukocyte-associated Ig-like receptor-1 has SH2 domain-containing phosphatase-independent function and recruits C-terminal Src kinase
Leukocyte-associated Ig-like receptor-1 has SH2 domain-containing phosphatase-independent function and recruits C-terminal Src kinase
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DOI：
10.1002/eji.200535226
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发表时间：
2006-01-01
影响因子：
5.4
通讯作者：
Meyaard, L
中科院分区：
文献类型：
--
作者：
Verbrugge, A;Rijkers, ESK;Meyaard, L
免疫系统中的大多数抑制性受体含有一个或几个基于免疫受体酪氨酸的抑制性基序（ITIM），并募集含有SH 2结构域的磷酸酶SHP-1、SHP-2和/或SHIP，它们通常被认为是抑制功能所必需的。然而，还没有系统地研究ITIM承载受体是否通过替代相互作用发挥其功能。在这里，我们描述了白细胞相关免疫球蛋白样受体（LAIR）-1在缺乏SHP-1和SHP-2的DT 40鸡B细胞中具有抑制功能。此外，我们发现LAIR-1在磷酸化后不招募SHIP。因此，LAIR-1可以独立于含有SH 2结构域的磷酸酶发挥作用，并且必须募集至少一种其他信号分子。利用酵母三杂交系统，我们发现磷酸化LAIR-1结合的C-末端Src激酶（Csk）。这种相互作用需要Csk的SH 2结构域和LAIR-1的N-末端ITIM中酪氨酸的磷酸化。我们建议，Csk是一个额外的球员在调节免疫系统的ITIM轴承受体。
Most inhibitory receptors in the immune system contain one or several immunoreceptor tyrosine-based inhibitory motifs (ITIM) and recruit the SH2 domain-containing phosphatases SHP-1, SHP-2 and/or SHIP, which are generally believed to be essential for the inhibitory function. However, it has not been systematically investigated whether ITIM-bearing receptors exert their function through alternative interactions. Here we describe that leukocyte-associated Ig-like receptor (LAIR)-1 has inhibitory function in DT40 chicken B cells that lack both SHP-1 and SHP-2. In addition, we found that LAIR-1 did not recruit SHIP upon phosphorylation. Thus, LAIR-1 can function independently from SH2 domain-containing phosphatases and must recruit at least one other signaling molecule. Using a yeast-tri-hybrid system, we found that phosphorylated LAIR-1 bound the C-terminal Src kinase (Csk). The interaction required the SH2 domain of Csk and phosphorylation of the tyrosine in the N-terminal ITIM of LAIR-1. We propose that Csk is an additional player in the regulation of the immune system by ITIM-bearing receptors.