Toll-like Receptor 9 (D2C9) Rabbit mAb

• 产品编号：CST-5845S      品牌：CST       原厂货号：5845S
• 产品分类：抗体 > 一抗 > 蛋白特异性一抗
• 应用分类：

描述：

Toll-like Receptor 9 (D2C9) Rabbit mAb兔单抗能够检测内源水平TLR9蛋白总体水平。此抗体预计只能与全长得TLR9蛋白反应，而不与其他剪切形式的TLR9蛋白交叉反应。此单克隆抗体是通过合成人源对应的TLR9 中间位置周围的肽段来免疫动物而获得。Toll样受体(TLR) 家族成员, 是因与其密切相关的果蝇Toll受体而命名的，TLR在天然免疫中发挥了极其重要的作用(1-3)。TLRs 能够识别不同病原菌中保守的结构域并介导防御反应。TLR的触发导致了NF-κB信号通路的激活并因此调控下游的免疫和炎症基因的表达。TLRs与IL-1受体家族都包含一个大约200个氨基酸的保守区域—TIR结构域。受到激活后，TLRs 与细胞质中的含有TIR区域的一系列接头蛋白作用，包括MyD88 (myeloid differentiation factor), MAL/TIRAP (MyD88-adaptor-like/TIR-associated protein), TRIF (Toll-receptor-associated activator of interferon), and TRAM (Toll-receptor-associated molecule)。这些反应导致了IRAK1 和 IRAK4的招募和激活，并与TRAF6 形成复合体激活 TAK1 和 IKK。IKK的激活导致了正常情况下截留NF-κB在细胞质中而失去活性的IκB的降解。TLR9在巨噬细胞，树突状细胞和B淋巴细胞中高表达, 人源性的TLR9通过不同的剪切形式形成五个亚型(4,5)。TLR9结合到细菌DNA中未甲基化的CpG岛上并通过MyD88而激活 NF-κB (6-8)。与 TLR 家族的其他成员定位于质膜相反, TLR9 在静止细胞中作为胞内受体定位于ER (9)。当结合到CpG DNA上, TLR9 经过蛋白酶水解过程并转移到内溶酶体上并与MyD88结合起始下游的信号通路(10-12)。

1. Akira, S. (2003) J Biol Chem 278, 38105-8.
2. Beutler, B. (2004) Nature 430, 257-63.
3. Dunne, A. and O'Neill, L.A. (2003) Sci STKE 2003, re3.
4. Medzhitov, R. et al. (1997) Nature 388, 394-7.
5. Schwandner, R. et al. (1999) J Biol Chem 274, 17406-9.
6. Takeuchi, O. et al. (1999) Immunity 11, 443-51.
7. Alexopoulou, L. et al. (2001) Nature 413, 732-8.
8. Zhang, F.X. et al. (1999) J Biol Chem 274, 7611-4.
9. Horng, T. et al. (2001) Nat Immunol 2, 835-41.
10. Oshiumi, H. et al. (2003) Nat Immunol 4, 161-7.
11. Muzio, M. et al. (1997) Science 278, 1612-5.
12. Wesche, H. et al. (1997) Immunity 7, 837-47.
13. Suzuki, N. et al. (2002) Nature 416, 750-6.
14. Irie, T. et al. (2000) FEBS Lett 467, 160-4.
15. Du, X. et al. (2000) Eur Cytokine Netw 11, 362-71.
16. Chuang, T.H. and Ulevitch, R.J. (2000) Eur Cytokine Netw 11, 372-8.
17. Hemmi, H. et al. (2000) Nature 408, 740-5.
18. Bauer, S. et al. (2001) Proc Natl Acad Sci U S A 98, 9237-42.
19. Takeshita, F. et al. (2001) J Immunol 167, 3555-8.
20. Latz, E. et al. (2004) Nat Immunol 5, 190-8.
21. Park, B. et al. (2008) Nat Immunol 9, 1407-14.
22. Ewald, S.E. et al. (2008) Nature 456, 658-62.
23. Sepulveda, F.E. et al. (2009) Immunity 31, 737-48.

原厂资料：

Specificity / Sensitivity

Toll-like Receptor 9 (D2C9) Rabbit mAb recognizes endogenous levels of total TLR9 protein. This antibody is predicted to react with known full-length isoforms of TLR9, but not with the cleaved TLR9 protein.

Source / Purification

Monoclonal antibody is produced by immunizing animals with recombinant protein specific to the central ectodomain of human TLR9 protein.

Background

Members of the Toll-like receptor (TLR) family, named for the closely related Toll receptor in Drosophila, play a pivotal role in innate immune responses (1-3). TLRs recognize conserved motifs found in various pathogens and mediate defense responses. Triggering of the TLR pathway leads to the activation of NF-κB and subsequent regulation of immune and inflammatory genes. The TLRs and members of the IL-1 receptor family share a conserved stretch of approximately 200 amino acids known as the TIR domain. Upon activation, TLRs associate with a number of cytoplasmic adaptor proteins containing TIR domains including MyD88 (myeloid differentiation factor), MAL/TIRAP (MyD88-adaptor-like/TIR-associated protein), TRIF (Toll-receptor-associated activator of interferon), and TRAM (Toll-receptor-associated molecule). This association leads to the recruitment and activation of IRAK1 and IRAK4, which form a complex with TRAF6 to activate TAK1 and IKK. Activation of IKK leads to the degradation of IκB that normally maintains NF-κB inactivity by sequestering it in the cytoplasm.TLR9 is highly expressed in macrophages, dendritic cells, and B lymphocytes, and in humans has five isoforms generated by alternative splicing (4,5). TLR9 binds to unmethylated CpG motifs present on bacterial DNA and stimulates NF-κB via the MyD88 adaptor protein (6-8). In contrast to most TLR family members that are localized to the plasma membrane, TLR9 is an intracellular receptor localized to the ER in resting cells (9). Upon binding to CpG DNA, TLR9 is proteolytically processed and translocates to endo-lysosomal compartments where it binds MyD88, initiating downstream signaling (10-12).

1. Akira, S. (2003) J Biol Chem 278, 38105-8.
2. Beutler, B. (2004) Nature 430, 257-63.
3. Dunne, A. and O'Neill, L.A. (2003) Sci STKE 2003, re3.
4. Medzhitov, R. et al. (1997) Nature 388, 394-7.
5. Schwandner, R. et al. (1999) J Biol Chem 274, 17406-9.
6. Takeuchi, O. et al. (1999) Immunity 11, 443-51.
7. Alexopoulou, L. et al. (2001) Nature 413, 732-8.
8. Zhang, F.X. et al. (1999) J Biol Chem 274, 7611-4.
9. Horng, T. et al. (2001) Nat Immunol 2, 835-41.
10. Oshiumi, H. et al. (2003) Nat Immunol 4, 161-7.
11. Muzio, M. et al. (1997) Science 278, 1612-5.
12. Wesche, H. et al. (1997) Immunity 7, 837-47.
13. Suzuki, N. et al. (2002) Nature 416, 750-6.
14. Irie, T. et al. (2000) FEBS Lett 467, 160-4.
15. Du, X. et al. (2000) Eur Cytokine Netw 11, 362-71.
16. Chuang, T.H. and Ulevitch, R.J. (2000) Eur Cytokine Netw 11, 372-8.
17. Hemmi, H. et al. (2000) Nature 408, 740-5.
18. Bauer, S. et al. (2001) Proc Natl Acad Sci U S A 98, 9237-42.
19. Takeshita, F. et al. (2001) J Immunol 167, 3555-8.
20. Latz, E. et al. (2004) Nat Immunol 5, 190-8.
21. Park, B. et al. (2008) Nat Immunol 9, 1407-14.
22. Ewald, S.E. et al. (2008) Nature 456, 658-62.
23. Sepulveda, F.E. et al. (2009) Immunity 31, 737-48.

注意事项：

Storage: Supplied in 10 mM sodium HEPES (pH 7.5), 150
mM NaCl, 100 µg/ml BSA, 50% glycerol and less than 0.02%
sodium azide. Store at –20°C. Do not aliquot the antibody