IRAK Isoform Antibody Sampler Kit

• 产品编号：CST-4769S      品牌：Cell Signaling Technology       原厂货号：4769S
• 产品分类：抗体 > 一抗 > 复合抗体试剂盒
• 应用分类：

描述：

IRAK Isoform Antibody Sampler Kit 中的每一个抗体都能检测其目标蛋白的内源水平蛋白。在内源水平上并未发现抗体与其它家族成员有交叉反应。抗体是通过合成鼠科对应的IRAK1 C-末端周围的肽段，人源IRAK2，人源IRAK-M，人源IRAK4 Lys41位点周围的肽段来免疫动物而获得。IRAK Isoform Antibody Sampler Kit为研究4个IL-1受体相关激酶家族成员 IRAK1, IRAK2, IRAK3/IRAK-M 和 IRAK4的总蛋白水平提供了经济有效的方法。细胞白介素1(IL-1)受体相关激酶(IRAK)是丝氨酸/酪氨酸特异性的激酶，它通过IL-1诱导的方式与IL-1发生共沉淀(1)。 哺乳动物的IRAK家族有四个成员(IRAK1, IRAK2, IRAK3/IRAK-M and IRAK4)。IL-1结合到IL-1的I类受体(IL-1RI)而起始包含IL-1RI, AcP, MyD88和IRAKs的复合体(2)。IRAK在IL-1刺激后能够在短时间内自磷酸化。接着IRAK从IL-1RI复合体上解离，泛素化并与两个膜结合蛋白 TAB2 和TRAF6结合。IRAK-TRAF6-TAB2复合体释放到细胞质中并激活蛋白激酶的级联反应，包括TAK1、IKKs 和应激激活激酶 (3)。与IL-1R/TLR (Toll样受体)连接后, IRAK1和IRAK4通过转换器蛋白MyD88而迅速的招募到受体上(4)。IRAK1通过IRAK4在Thr209 和 Thr387位点磷酸化 (5), 紧接着在多个不同域自磷酸化。与IRAK1和 IRAK4不同, IRAK2 和IRAK-M并不具有重要的激酶活性，尽管他们在过表达后也能激活NF-κB(6,7)。针对IRAK2的反义核酸链能抑制IL-1介导的NF-κB的激活(8)。与家族中的其它成员相比，IRAK-M的表达更为局限，只是在单核细胞/巨噬细胞中高表达(6)。研究IRAK-M敲除小鼠表明，IRAK-M在Toll样受体信号通路和天然免疫应答中作为负调控因子，它们是通过阻止IRAK1和IRAK4与MyD88的解体并接下来与TRAF6形成复合体而实现上述功能(9)。

1. Dinarello, C.A. (1996) Blood 87, 2095-147.
2. Takaesu, G. et al. (2001) Mol Cell Biol 21, 2475-84.
3. Janssens, S. and Beyaert, R. (2003) Mol Cell 11, 293-302.
4. Gottipati, S. et al. (2008) Cell Signal 20, 269-76.
5. Kollewe, C. et al. (2004) J Biol Chem 279, 5227-36.
6. Wesche, H. et al. (1999) J Biol Chem 274, 19403-10.
7. Muzio, M. et al. (1997) Science 278, 1612-5.
8. Guo, F. et al. (1999) Inflammation 23, 535-43.
9. Kobayashi, K. et al. (2002) Cell 110, 191-202.

原厂资料：

Specificity / Sensitivity

Each antibody in the IRAK Isoform Antibody Sampler Kit detects endogenous levels of its indicated target. Cross-reactivity has not been detected with other family members at endogenous levels.

Source / Purification

Antibodies are produced by immunizing animals with a synthetic peptide corresponding to residues near the carboxy-terminus of murine IRAK1, human IRAK2, human IRAK-M, and surrounding Lys41 of human IRAK4.

Description

The IRAK Isoform Antibody Sampler Kit provides an economical means to examine total protein levels of the four Interleukin-1 Receptor Associated Kinase family members: IRAK1, IRAK2, IRAK3/IRAK-M, and IRAK4.

Background

Interleukin-1 (IL-1) receptor-associated kinase (IRAK) is a serine/threonine-specific kinase that can be coprecipitated in an IL-1-inducible manner with the IL-1 receptor (1). The mammalian family of IRAK molecules contains four members (IRAK1, IRAK2, IRAK3/IRAK-M and IRAK4). The binding of IL-1 to IL-1 receptor type I (IL-1RI) initiates the formation of a complex that includes IL-1RI, AcP, MyD88 and IRAKs (2). IRAK undergoes autophosphorylation shortly after IL-1 stimulation. The subsequent events involve IRAK dissociation from the IL-1RI complex, its ubiquitination and its association with two membrane-bound proteins: TAB2 and TRAF6. The resulting IRAK-TRAF6-TAB2 complex is then released into the cytoplasm and activates protein kinase cascades, which include TAK1, IKKs and the stress-activated kinases (3).Upon IL-1R/TLR (Toll-Like Receptor) ligation, IRAK1 and IRAK4 are rapidly recruited to the receptor by the adaptor MyD88 (4). IRAK1 is phosphorylated by IRAK4 at Thr209 and Thr387 (5), followed by sequential autohyperphosphorylation in various domains. Unlike IRAK1 and IRAK4, IRAK2 and IRAK-M do not have significant kinase activity although they can still activate NF-κB when overexpressed (6,7). Antisense oligonucleotide depletion of IRAK2 can inhibit IL-1 mediated NF-κB activation (8). Expression of IRAK-M is more restricted compared to other family members with highest levels of expression occurring in monocytes/macrophages (6). Studies from IRAK-M knockout mice suggest that it may play a role as a negative regulator of TLR signaling and innate immune responses by preventing the dissociation of IRAK1 and IRAK4 from MyD88 and the subsequent formation of its complex with TRAF6 (9).

1. Dinarello, C.A. (1996) Blood 87, 2095-147.
2. Takaesu, G. et al. (2001) Mol Cell Biol 21, 2475-84.
3. Janssens, S. and Beyaert, R. (2003) Mol Cell 11, 293-302.
4. Gottipati, S. et al. (2008) Cell Signal 20, 269-76.
5. Kollewe, C. et al. (2004) J Biol Chem 279, 5227-36.
6. Wesche, H. et al. (1999) J Biol Chem 274, 19403-10.
7. Muzio, M. et al. (1997) Science 278, 1612-5.
8. Guo, F. et al. (1999) Inflammation 23, 535-43.
9. Kobayashi, K. et al. (2002) Cell 110, 191-202.

注意事项：

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