Phospho-ASK1 (Ser83) Antibody

• 产品编号：CST-3761S      品牌：CST       原厂货号：3761S
• 产品分类：抗体 > 一抗 > 磷酸化抗体
• 应用分类：

描述：

Phospho-ASK1 (Ser83)兔多抗能检测转染水平的Ser83位点磷酸化的ASK1蛋白。该多克隆抗体是采用合成的与人源ASK1蛋白氨Ser83位点周围残基相一致的磷酸化肽段免疫动物而获得。该抗体经蛋白A和肽亲和层析纯化。凋亡信号调节激酶1（ASK1）是一种MAPKKK，在应激诱导的凋亡中起着关键的作用(1,2)。ASK1蛋白在多种应激相关的刺激因子作用下被激活，内在机制各不相同。ASK1蛋白能够活化MKK4、MKK3，进而激活JNK和p38蛋白（3）。ASK1蛋白的过度表达能激活JNK和p38蛋白，并通过涉及线粒体细胞死亡途径的信号而诱导多种细胞凋亡(4,5)。来源于ASK1-/- 小鼠的胚胎成纤维细胞或初级神经元细胞对应激诱导的JNK和p38蛋白活化和细胞死亡有拮抗作用。ASK1蛋白Ser967位点的磷酸化对其与14-3-3蛋白的结合和抑制细胞死亡十分重要(6)。氧化应激能够诱导ASK1蛋白Ser967位点的去磷酸化及活化环中的Thr845位点的磷酸化，这两个变化与ASK1蛋白活性和ASK1依赖型细胞凋亡相关(7,8)。另一方面，Akt蛋白能将ASK1蛋白Ser83位点磷酸化，从而减弱ASK1蛋白的活力并促进细胞存活（9）。ASK1蛋白是Akt激酶的底物，磷酸化位点是Ser83位点，该磷酸化过程与刺激后的ASK1激酶活力降低有关（6）。

1. Ichijo, H. et al. (1997) Science 275, 90-94.
2. Wang, X.S. et al. (1996) J. Biol. Chem. 271, 31607-31611.
3. Matsuzawa, A. and Ichijo, H. (2001) J. Biochem. (Tokyo) 130, 1-8.
4. Tobiume, K. et al. (2001) EMBO Rep. 2, 222-228.
5. Nishitoh, H. et al. (2002) Genes Dev. 16, 1345-1355.
6. Zhang, L. et al. (1999) Proc. Natl. Acad. Sci. USA 96, 8511-8515.
7. Tobiume, K. et al. (2002) J. Cell. Physiol. 191, 95-104.
8. Goldman, E.H. et al. (2004) J. Biol. Chem. in press, .
9. Kim, A.H. et al. (2001) Mol. Cell. Biol. 21, 893-901.

原厂资料：

Specificity / Sensitivity

Phospho-ASK1 (Ser83) Antibody detects transfected ASK1 only when phosphorylated at Ser83.

Source / Purification

Polyclonal antibodies are produced by immunizing animals with a synthetic phosphopeptide corresponding to residues around Ser83 of human ASK1. Antibodies are purified by protein A and peptide affinity chromatography.

Background

Apoptosis signal-regulating kinase 1 (ASK1), a MAP kinase kinase kinase, plays essential roles in stress-induced apoptosis (1,2). ASK1 is activated in response to a variety of stress-related stimuli through distinct mechanisms and activates MKK4 and MKK3, which in turn activate JNK and p38 (3). Overexpression of ASK1 activates JNK and p38 and induces apoptosis in several cell types through signals involving the mitochondrial cell death pathway. Embryonic fibroblasts or primary neurons derived from ASK1-/- mice are resistant to stress-induced JNK and p38 activation and cell death (4,5). Phosphorylation at Ser967 is essential for ASK1 association with 14-3-3 protein and suppression of cell death (6). Oxidative stress induces dephosphorylation of Ser967 and phosphorylation of Thr845 in the activation loop of ASK1, and both are correlated with ASK1 activity and ASK1-dependent apoptosis (7,8). On the other hand, Akt phosphorylates ASK1 at Ser83, which attenuates ASK1 activity and promotes cell survival (9).

ASK1 is a substrate for phosphorylation at Ser83 by Akt, and that this phosphorylation is associated with a decrease in stimulated ASK1 kinase activity (6).

1. Ichijo, H. et al. (1997) Science 275, 90-94.
2. Wang, X.S. et al. (1996) J. Biol. Chem. 271, 31607-31611.
3. Matsuzawa, A. and Ichijo, H. (2001) J. Biochem. (Tokyo) 130, 1-8.
4. Tobiume, K. et al. (2001) EMBO Rep. 2, 222-228.
5. Nishitoh, H. et al. (2002) Genes Dev. 16, 1345-1355.
6. Zhang, L. et al. (1999) Proc. Natl. Acad. Sci. USA 96, 8511-8515.
7. Tobiume, K. et al. (2002) J. Cell. Physiol. 191, 95-104.
8. Goldman, E.H. et al. (2004) J. Biol. Chem. in press, .
9. Kim, A.H. et al. (2001) Mol. Cell. Biol. 21, 893-901.

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.