Structure, expression pattern and biological activity of molecular complex TREM-2/DAP12
Structure, expression pattern and biological activity of molecular complex TREM-2/DAP12
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DOI：
10.1016/j.humimm.2013.02.003
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发表时间：
2013-06-01
期刊：
影响因子：
2.7
通讯作者：
Jurkowska, Monika
中科院分区：
文献类型：
--
作者：
Paradowska-Gorycka, Agnieszka;Jurkowska, Monika
12 kDa的DNA激活蛋白（DAP 12）是I型跨膜衔接蛋白的成员，含有基于免疫受体酪氨酸的激活基序（ITAM）。在人类中，DAP 12基因位于染色体19q13.1上。DAP 12与髓样细胞上表达的触发受体2（TREM-2）形成分子复合物。TREM-2连接导致Src家族激酶的活化、DAP 12的ITAM中酪氨酸残基的磷酸化、Syk和ZAP 70酪氨酸激酶的募集以及胞内信号级联的起始。根据细胞类型，DAP 12/TREM-2活化在破骨细胞的活化和分化、细菌的吞噬作用、脑和骨稳态以及巨噬细胞和树突状细胞中toll样受体（TLR）信号传导的抑制中起重要作用。由于TREM-2配体的性质不明确，人们对这种复杂受体的功能认识受到限制，本文综述了DAP 12及其相关受体TREM-2的结构、生物学功能和信号通路。(c)2013年美国组织相容性和免疫遗传学学会。爱思唯尔公司出版All rights reserved.
DNAX-activating protein of 12 kDa (DAP12) is a member of type I transmembrane adapter proteins containing immunoreceptor tyrosine-based activation motifs (ITAMs). In humans DAP12 gene is located on chromosome 19q13.1. DAP12 forms a molecular complex with triggering receptor expressed on myeloid cells two (TREM-2). TREM-2 ligation leads to the activation of Src family kinases, phosphorylation of tyrosine residues in the ITAM of DAP12, recruitment of the Syk and ZAP70 tyrosine kinases and initiation of an intracellular signaling cascade. Depending on the cell type, DAP12/TREM-2 activation plays an important role in activation and differentiation of osteoclasts, phagocytosis of bacteria, brain and bone homeostasis and inhibition of the toll-like receptor (TLR) signaling in macrophages and dendritic cells. A proper understanding of the function of this complex receptor has been restrained because of the elusive nature of TREM-2 ligands.Here we review the structure, biological functions and signaling pathways of DAP12 and its associated receptor TREM-2. (c) 2013 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.