Phospho-CAD (Ser1859) Antibody

• 产品编号：CST-12662S      品牌：CST       原厂货号：12662S
• 产品分类：抗体 > 一抗 > 磷酸化抗体
• 应用分类：

描述：

Phospho-CAD (Ser1859) Antibody只检测丝氨酸1859位发生磷酸化的内源性CAD蛋白水平。该多克隆抗体是由合成的人源CAD蛋白丝氨酸(2481位)肽段免疫动物而制备的。抗体由protein A和肽亲和层析技术纯化。CAD蛋白对于嘧啶核苷酸的从头合成过程必不可少，它具有下列酶的活性：谷氨酰胺酰胺转移酶，氨甲酰磷酸合成酶，天冬氨酸转氨甲酰酶和二氢乳清酸酶。因此，CAD能够将谷氨酰胺转换为尿苷酸，后者是所有嘧啶碱基的一个共同前体，它对于核酸的合成也是必需的（1）。在静息细胞中，CAD主要定位于细胞质中负责合成嘧啶。当增殖细胞进入S期，MAP激酶（ERK1 / 2）催化CAD蛋白Thr456位磷酸化，使CAD易位到细胞核。当细胞退出S期，CAD 的Thr456位去磷酸化，Ser1406位在PKA作用下磷酸化，返回通路恢复基础活性（2）。各种研究表明CAD在几种类型的癌症中表达增加，促进了药理抑制剂如PALA的开发。进一步的研究已经将CAD确定为一个潜在的预测早期前列腺癌的复发标记（3）。mTORC1的是一种蛋白激酶，通过感知和整合各种生长信号来调节细胞的生长和增殖。 S6激酶1（S6K1）是mTORC1靶向调节的一个下游核糖体蛋白，直接磷酸化CAD蛋白1859位丝氨酸。这种磷酸化作用刺激了嘧啶从头合成的前三个步骤，从而有助于促进细胞经历细胞周期S期的整体进程（4,5）

1. Coleman, P.F. et al. (1977) J Biol Chem 252, 6379-85.
2. Sigoillot, F.D. et al. (2005) J Biol Chem 280, 25611-20.
3. Morin, A. et al. (2012) FASEB J 26, 460-7.
4. Ben-Sahra, I. et al. (2013) Science 339, 1323-8.
5. Robitaille, A.M. et al. (2013) Science 339, 1320-3.

原厂资料：

Specificity / Sensitivity

Phospho-CAD (Ser1859) Antibody recognizes endogenous levels of CAD protein only when phosphorylated at Ser1859.

Source / Purification

Polyclonal antibodies are produced by immunizing animals with a synthetic peptide corresponding to residues surrounding Ser1859 of human CAD protein. Antibodies are purified by protein A and peptide affinity chromatography.

Background

CAD is essential for the de novo synthesis of pyrimidine nucleotides and possesses the following enzymatic activities: glutamine amidotransferase, carbamoyl-phosphate synthetase, aspartate transcarbamoylase, and dihydroorotase. Thus, the enzyme converts glutamine to uridine monophosphate, a common precursor of all pyrimidine bases, and it is necessary for nucleic acid synthesis (1). In resting cells, CAD is localized mainly in the cytoplasm where it carries out pyrimidine synthesis. As proliferating cells enter S phase, MAP Kinase (Erk1/2) phosphorlyates CAD at Thr456, resulting in CAD translocation to the nucleus. As cells exit S phase, CAD is dephosphorylated at Thr456 and phosphorylated at Ser1406 by PKA, returning the pathway to basal activity (2). Various research studies have shown increased expression of CAD in several types of cancer, prompting the development of pharmacological inhibitors such as PALA. Further studies have identified CAD as a potential predictive early marker of prostate cancer relapse (3).mTORC1 is a protein kinase that works to regulate the growth and proliferation of cells by sensing and integrating various growth signals. S6 kinase 1 (S6K1) is a downstream ribosomal protein target of mTORC1 and directly phosphorylates Ser1859 on CAD. This phosphorylation stimulates the first three steps of the de novo primidine synthesis and thus helps to advance the cells overall progression through S phase of the cell cycle (4,5).

1. Coleman, P.F. et al. (1977) J Biol Chem 252, 6379-85.
2. Sigoillot, F.D. et al. (2005) J Biol Chem 280, 25611-20.
3. Morin, A. et al. (2012) FASEB J 26, 460-7.
4. Ben-Sahra, I. et al. (2013) Science 339, 1323-8.
5. Robitaille, A.M. et al. (2013) Science 339, 1320-3.

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.
*Species cross-reactivity is determined by western blot.
** Anti-rabbit secondary antibodies must be used to detect this antibody.