CMRF-35-like molecule-1, a novel mouse myeloid receptor, can inhibit osteoclast formation
CMRF-35-like molecule-1, a novel mouse myeloid receptor, can inhibit osteoclast formation
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DOI：
10.4049/jimmunol.171.12.6541
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发表时间：
2003-12-15
影响因子：
4.4
通讯作者：
Daws, MR
中科院分区：
文献类型：
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作者：
Chung, DH;Humphrey, MB;Daws, MR
通过与髓细胞-2表达的触发受体同源性，筛选小鼠表达序列标签数据库，分离出一个新的单一Ig结构域受体，并对其进行了表达和表征。该受体与人类CMRF-35受体序列最为相似，因此我们将其命名为CMRF-35样分子(CLM)-1。通过筛选小鼠基因组，我们确定CLM-1是位于小鼠11号染色体一小段的多基因家族的一部分。每个都包含一个单一的Ig结构域，它们主要在髓系细胞中表达。CLM-1含有多个细胞质酪氨酸残基，包括两个基于免疫受体酪氨酸的抑制基序，我们证明CLM-1可以与含有磷酸酶-1的Src-homology 2结合。通过NF-KB配体受体激活剂（RANKL）（一种驱动破骨细胞形成的细胞因子）处理，CLM-1 mRNA的表达下调。此外，CLM-1在破骨细胞系RAW （RAW.CLM-1）中的表达可阻止RANKL和tgf - β诱导的破骨细胞生成。生的。CLM-1细胞不能多核，也不能上调降钙素受体，但它们表达抗酒石酸酸性磷酸酶、组织蛋白酶K和β(3)整合素，表明破骨细胞的发生在中后期被阻断。因此，我们定义了一个新的髓系受体家族，并证明该家族的第一个成员CLM-1是一种抑制性受体，能够阻断破骨细胞的发生。
By homology to triggering receptor expressed by myeloid cells-2, we screened the mouse expressed sequence tag database and isolated a new single Ig domain receptor, which we have expressed and characterized. The receptor is most similar in sequence to the human CMRF-35 receptor, and thus we have named it CMRF-35-like molecule (CLM)-1. By screening the mouse genome, we determined that CLM-1 was part of a multigene family located on a small segment of mouse chromosome 11. Each contains a single Ig domain, and they are expressed mainly in cells of the myeloid lineage. CLM-1 contains multiple cytoplasmic tyrosine residues, including two that lie in consensus immunoreceptor tyrosine-based inhibitory motifs, and we demonstrate that CLM-1 can associate with Src-homology 2 containing phosphatase-1. Expression of CLM-1 mRNA is down-regulated by treatment with receptor activator of NF-KB ligand (RANKL), a cytokine that drives osteoclast formation. Furthermore, expression of CLM-1 in the osteoclastogenic cell line RAW (RAW.CLM-1) prevents osteoclastogenesis induced by RANKL and TGF-beta. RAW.CLM-1 cells fail to multinucleate and do not up-regulate calcitonin receptor, but they express tartrate-resistant acid phosphatase, cathepsin K, and beta(3) integrin, suggesting that osteoclastogenesis is blocked at a late-intermediate stage. Thus, we define a new family of myeloid receptors, and demonstrate that the first member of this family, CLM-1, is an inhibitory receptor, able to block osteoclastogenesis.