Identification of phosphatidylserine as a ligand for the CD300a immunoreceptor

Identification of phosphatidylserine as a ligand for the CD300a immunoreceptor
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DOI:
10.1016/j.bbrc.2011.12.025
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发表时间:
2012-01-06
影响因子:
3.1
通讯作者:
Shibuya, Akira
Shibuya, Akira
中科院分区:
生物学4区
文献类型:
--
作者:
Nakahashi-Oda, Chigusa;Tahara-Hanaoka, Satoko;Shibuya, Akira

文献摘要

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CD 300 a是CD 300家族分子的成员,由人17号染色体上的7个基因和小鼠11号染色体上的9个基因组成。CD 300 a具有长的胞质区域,其含有基于酪氨酸的共有免疫受体抑制基序(ITIM)序列。在与针对CD 300 a的抗体交联后,CD 300 a介导骨髓细胞中的抑制信号。然而,CD 300 a的配体尚未被鉴定,CD 300 a的生理作用仍不清楚。在这里,我们证明了嵌合融合蛋白的CD 300 a细胞外结构域与Fc部分的人IgG特异性结合的磷脂酰丝氨酸(PS),这是暴露在细胞凋亡细胞的质膜的外部小叶。PS与CD 300 a的结合诱导肥大细胞对LPS应答时CD 300 a募集SHP-1。这些结果表明,CD 300 a是一种新的PS受体。(C)2011 Elsevier Inc. All rights reserved.
CD300a is a member of CD300 family molecules consisting of seven genes on human chromosome 17 and nine genes in mouse chromosome 11. CD300a has a long cytoplasmic region containing the consensus immunoreceptor tyrosine-based inhibitory motif (ITIM) sequence. Upon crosslinking with antibodies against CD300a, CD300a mediates an inhibitory signal in myeloid cells. However, the ligand for CD300a has not been identified and the physiological role of CD300a remained unclear. Here, we demonstrate that the chimeric fusion protein of CD300a extracellular domain with the Fc portion of human IgG specifically bound phosphatidylserine (PS), which is exposed on the outer leaflet of the plasma membrane of apoptotic cells. PS binding to CD300a induced SHP-1 recruitment by CD300a in mast cells in response to LPS. These results indicated that CD300a is a new PS receptor. (C) 2011 Elsevier Inc. All rights reserved.