Phospho-AS160 (Thr642) (D27E6) Rabbit mAb

• 产品编号：CST-8881S      品牌：CST       原厂货号：8881S
• 产品分类：抗体 > 一抗 > 磷酸化抗体
• 应用分类：

描述：

Phospho-AS160 (Thr642) (D27E6) Rabbit mAb兔单抗仅能够检测内源性642位苏氨酸发生磷酸化的AS160蛋白水平。该单克隆抗体是由人源AS160蛋白苏氨酸(642位)磷酸化肽段免疫动物而制备的。胰岛素是控制能量代谢如糖脂代谢的一种主要激素。胰岛素结合并激活胰岛素受体（IR）酪氨酸激酶，后者能够招募并磷酸化各种接头蛋白。在骨胳肌细胞和脂肪细胞中，通过将GLUT4葡萄糖转运小体从胞浆转运到质膜，胰岛素及其受体引发的信号通路可以增加细胞对的糖的摄入 (1)。有一种分子量为160 kDa的AKt丝氨酸/苏氨酸激酶底物(AS160, TBC1D4)是一种带有Rab GTP酶活性的蛋白，它可以调节胰岛素介导的Glut4转运。AS160在多种组织中表达，包括大脑，肾脏，肝脏，白色脂肪及棕色脂肪(2)。在体内，已经鉴定出多个AS160蛋白的AKt激酶磷酸化位点，其中的五个位点(Ser318, Ser570, Ser588, Thr642和Thr751)，在用胰岛素处理后，磷酸化水平增加(2, 3)。一些针对重组AS160蛋白的研究结果表明，胰岛素诱导AS160磷酸化是Glut4的转运过程中的一个重要步骤(3)，并且在2型糖尿病中，该蛋白的磷酸化水平降低(4)。14-3-3调节蛋白与Thr642位点磷酸化AS160蛋白的结合是GLUT4的转运过程中的一个必需步骤(5)。在对浓度诱导的Glut4转运调控中，AMPK对AS160的磷酸化作用也与之相关(6)。

1. Watson, R.T. and Pessin, J.E. (2006) Trends Biochem. Sci. 31, 215-222.
2. Kane, S. et al. (2002) J. Biol. Chem. 277, 22115-22118.
3. Sano, H. et al. (2003) J. Biol. Chem. 278, 14599-14602.
4. Karlsson, H.K. et al. (2005) Diabetes 54, 1692-1697.
5. Ramm, G. et al. (2006) J. Biol. Chem. 281, 29174-29180.
6. Kramer, H.F. et al. (2006) J. Biol. Chem. 281, 31478-31485.

原厂资料：

Specificity / Sensitivity

Phospho-AS160 (Thr642) (D27E6) Rabbit mAb recognizes endogenous levels of AS160 protein only when phosphorylated at Thr642.

Source / Purification

Monoclonal antibody is produced by immunizing animals with a synthetic phosphopeptide corresponding to residues surrounding Thr642 of human AS160 protein.

Background

Insulin is a major hormone controlling critical energy functions, such as glucose and lipid metabolism. Insulin binds to and activates the insulin receptor (IR) tyrosine kinase, which phosphorylates and recruits adaptor proteins. The signaling pathway initiated by insulin and its receptor stimulates glucose uptake in muscle cells and adipocytes through translocation of the Glut4 glucose transporter from the cytoplasm to the plasma membrane (1). A 160 kDa substrate of the Akt Ser/Thr kinase (AS160, TBC1D4) is a Rab GTPase-activating protein that regulates insulin-stimulated Glut4 trafficking. AS160 is expressed in many tissues including brain, kidney, liver, and brown and white fat (2). Multiple Akt phosphorylation sites have been identified on AS160 in vivo, with five sites (Ser318, Ser570, Ser588, Thr642, and Thr751) showing increased phosphorylation following insulin treatment (2,3). Studies using recombinant AS160 demonstrate that insulin-stimulated phosphorylation of AS160 is a crucial step in Glut4 translocation (3) and is reduced in some patients with type 2 diabetes (4). The interaction of 14-3-3 regulatory proteins with AS160 phosphorylated at Thr642 is a necessary step for Glut4 translocation (5). Phosphorylation of AS160 by AMPK is involved in the regulation of contraction-stimulated Glut4 translocation (6).

1. Watson, R.T. and Pessin, J.E. (2006) Trends Biochem. Sci. 31, 215-222.
2. Kane, S. et al. (2002) J. Biol. Chem. 277, 22115-22118.
3. Sano, H. et al. (2003) J. Biol. Chem. 278, 14599-14602.
4. Karlsson, H.K. et al. (2005) Diabetes 54, 1692-1697.
5. Ramm, G. et al. (2006) J. Biol. Chem. 281, 29174-29180.
6. Kramer, H.F. et al. (2006) J. Biol. Chem. 281, 31478-31485.

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.