Takeuchi O, Kawai T, Sanjo H, Copeland N G, Gilbert D J, Jenkins N A, Takeda K, Akira S
Department of Biochemistry, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo 663-8501, Japan.
Gene. 1999 Apr 29;231(1-2):59-65. doi: 10.1016/s0378-1119(99)00098-0.
Drosophila Toll protein is shown to activate the innate immune system in adult and regulate the dorsoventral patterning in the developing embryo. Recently, five human homologs of Drosophila Toll, designated as Toll-like receptors (TLRs), have been identified and shown to play a role in the innate immune response. We report here the molecular cloning and characterization of a new member of Toll-like receptor family, Toll-like receptor 6 (TLR6). Human and murine TLR6 are type-I transmembrane receptors that contain both an extracellular leucine-rich repeat (LRR) domain and a cytoplasmic Toll/IL-1 receptor (IL-1R)-like region. The amino acid sequence of human TLR6 (hTLR6) is most similar to that of hTLR1 with 69% identity. RT-PCR analysis revealed that murine TLR6 is expressed predominantly in spleen, thymus, ovary and lung. Like other TLR family members, constitutively active TLR6 activates both NF-kappaB and c-Jun N-terminal kinase (JNK). The TLR6 gene, as well as the TLR1 gene, mapped to the proximal region of murine chromosome 5 within 1.7cM of each other. These results suggest that TLR6 is a novel member of an expanding TLR family.
果蝇Toll蛋白可激活成虫的先天免疫系统,并调控发育中胚胎的背腹模式形成。最近,已鉴定出果蝇Toll的五个人类同源物,命名为Toll样受体(TLR),并证明其在先天免疫应答中发挥作用。我们在此报告Toll样受体家族新成员Toll样受体6(TLR6)的分子克隆及特性。人和鼠的TLR6是I型跨膜受体,包含一个细胞外富含亮氨酸重复序列(LRR)结构域和一个胞质Toll/白细胞介素-1受体(IL-1R)样区域。人TLR6(hTLR6)的氨基酸序列与hTLR1最为相似,一致性为69%。逆转录-聚合酶链反应(RT-PCR)分析显示,鼠TLR6主要在脾脏、胸腺、卵巢和肺中表达。与其他TLR家族成员一样,组成型活性TLR6可激活核因子κB(NF-κB)和c-Jun氨基末端激酶(JNK)。TLR6基因以及TLR1基因定位于鼠染色体5的近端区域,彼此相距1.7厘摩。这些结果表明,TLR6是不断扩大的TLR家族的一个新成员。