Phospho-IKKγ (Ser376) Antibody

• 产品编号：CST-2689S      品牌：CST       原厂货号：2689S
• 产品分类：抗体 > 一抗 > 磷酸化抗体
• 应用分类：

描述：

Phospho-IKKγ (Ser376) Antibody只能检测内源的在 Ser376位点磷酸化的IKKγ蛋白。多克隆抗体是通过合成人源对应的IKKγ Ser376位点周围的磷肽段来免疫动物而获得。抗体是通过protein A和多肽亲和层析法纯化。NF-κB/Rel转录调控因子在细胞质中与IκB抑制蛋白结合以非活性形式存在(1-3)。大部分激活因素采用通常信号通路即磷酸化诱导并通过蛋白水解酶体介导降解IκB的方法激活NF-κB (3-7)。此通路中最重要的步骤是激活高分子量的IκB激酶（IKK）复合体，此复合体催化的反应中有三个紧密相关的IKK亚基参与完成，IKKα and IKKβ 作为激酶的催化单元，IKKγ作为调控单元(8,9)。IKK的激活依赖于特定位点的磷酸化：IKKβ活性环中的 Ser177和Ser181位点以及IKKα中的serine 176 和 180 位点，这些位点的磷酸化引起蛋白构象的变化从而激活激酶（10-13）。经T细胞类型的病毒蛋白或经TNF-α 处理激活的NF-κB信号通路能够导致人源IKKβ依赖的主要在IKKγ Ser376位点的磷酸化 (14)。在小鼠中，将同源残基Ser369突变成丙氨酸后导致了IKKγ介导的刺激IKKβ激酶的激活的增强(15)。

1. Baeuerle, P.A. and Baltimore, D. (1988) Science 242, 540-6.
2. Beg, A.A. and Baldwin, A.S. (1993) Genes Dev 7, 2064-70.
3. Finco, T.S. et al. (1994) Proc Natl Acad Sci USA 91, 11884-8.
4. Brown, K. et al. (1995) Science 267, 1485-8.
5. Brockman, J.A. et al. (1995) Mol Cell Biol 15, 2809-18.
6. Traenckner, E.B. et al. (1995) EMBO J 14, 2876-83.
7. Chen, Z.J. et al. (1996) Cell 84, 853-62.
8. Zandi, E. et al. (1997) Cell 91, 243-52.
9. Karin, M. (1999) Oncogene 18, 6867-74.
10. DiDonato, J.A. et al. (1997) Nature 388, 548-54.
11. Mercurio, F. et al. (1997) Science 278, 860-6.
12. Johnson, L.N. et al. (1996) Cell 85, 149-58.
13. Delhase, M. et al. (1999) Science 284, 309-13.
14. Carter, R. S. et al. (2003) J. Biol. Chem. 278, 19642-19648.
15. Prajapati, S. and Gaynor, R.B. (2002) J. Biol. Chem. 277, 24331-24339.

原厂资料：

Specificity / Sensitivity

Phospho-IKKγ (Ser376) Antibody detects endogenous levels of IKKγ protein only when phosphorylated at Ser376.

Source / Purification

Polyclonal antibodies are produced by immunizing animals with a synthetic phosphopeptide corresponding to residues surrounding Ser376 of human IKKγ protein. Antibodies are purified by protein A and peptide affinity chromatography.

Background

The NF-κB/Rel transcription factors are present in the cytosol in an inactive state, complexed with the inhibitory IκB proteins (1-3). Most agents that activate NF-κB do so through a common pathway based on phosphorylation-induced, proteasome-mediated degradation of IκB (3-7). The key regulatory step in this pathway involves activation of a high molecular weight IκB kinase (IKK) complex, whose catalysis is generally carried out by three tightly associated IKK subunits. IKKα and IKKβ serve as the catalytic subunits of the kinase and IKKγ serves as the regulatory subunit (8,9). Activation of IKK depends upon phosphorylation; Ser177 and Ser181 in the activation loop of IKKβ (serine 176 and 180 in IKKα) are the specific sites whose phosphorylation causes conformational changes resulting in kinase activation (10-13).Activation of the NF-κB pathway by the T-cell lymphotrophic virus Tax protein or by TNF-α treatment leads to IKKβ-dependent phosphorylation of human IKKγ primarily at Ser376 (14). In mouse, mutation of the orthologous residue (Ser369) to alanine leads to enhanced IKKγ-mediated stimulation of IKKβ kinase activity (15).

1. Baeuerle, P.A. and Baltimore, D. (1988) Science 242, 540-6.
2. Beg, A.A. and Baldwin, A.S. (1993) Genes Dev 7, 2064-70.
3. Finco, T.S. et al. (1994) Proc Natl Acad Sci USA 91, 11884-8.
4. Brown, K. et al. (1995) Science 267, 1485-8.
5. Brockman, J.A. et al. (1995) Mol Cell Biol 15, 2809-18.
6. Traenckner, E.B. et al. (1995) EMBO J 14, 2876-83.
7. Chen, Z.J. et al. (1996) Cell 84, 853-62.
8. Zandi, E. et al. (1997) Cell 91, 243-52.
9. Karin, M. (1999) Oncogene 18, 6867-74.
10. DiDonato, J.A. et al. (1997) Nature 388, 548-54.
11. Mercurio, F. et al. (1997) Science 278, 860-6.
12. Johnson, L.N. et al. (1996) Cell 85, 149-58.
13. Delhase, M. et al. (1999) Science 284, 309-13.
14. Carter, R. S. et al. (2003) J. Biol. Chem. 278, 19642-19648.
15. Prajapati, S. and Gaynor, R.B. (2002) J. Biol. Chem. 277, 24331-24339.

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 antibody