Phospho-NEDD4L (Ser342) (D16D6) Rabbit mAb

• 产品编号：CST-12146S      品牌：CST       原厂货号：12146S
• 产品分类：抗体 > 一抗 > 磷酸化抗体
• 应用分类：

描述：

Phospho-NEDD4L (Ser342) (D16D6) Rabbit mAb兔单抗识别内源性的Ser342磷酸化的NEDD4L蛋白。该单克隆抗体经合成与人NEDD4L蛋白Ser342邻近氨基酸残基序列一致的肽段，免疫动物产生。NEDD4 (neural precursor expressed, developmentally down-regulated protein 4) 是最初在早期小鼠胚胎中枢神经系统中发现高度表达的一种基因(1)。随后，NEDD4类似蛋白家族在人类被确定包括7个成员(2)。NEDD4和NEDD4L蛋白包括多种功能结构域，包括钙依赖的磷脂和膜结合结构域(C2 domain)，两种到四种蛋白结合结构域(WW结构域)，以及一种E3泛素-蛋白连接酶结构域(HECT结构域)。NEDD4 和NEDD4L被证实可以下调神经电压控制的Na+离子通道(NaVs)，以及对上皮细胞内Na+浓度应答的上皮Na+通道(ENaCs) (3,4)。在多种NaV 和ENaC蛋白中发现，NEDD4的WW结构域与PY模序(PPXY的氨基酸序列)结合；这些蛋白的泛素化作用由NEDD4的HECT结构域介导，并可以导致它们的内摄作用并从胞质膜的移除。研究表明ENaC蛋白中PY模序的突变与Liddle's综合征有关，该疾病是高血压显性的一种变型(5)。除了靶向钠通道之外，NEDD4L被证实通过靶向Smad2蛋白的降解负向调控TGF-β信号通路（6）。在凋亡过程中，小鼠和人源的NEDD4蛋白能够被caspase蛋白迅速切割降解，尽管这种切割的意义尚不明确(7)。NEDD4L的 Ser342和Ser448可以被几种AGC激酶家族成员磷酸化，该家族成员包括SGK1, Akt, and PKA (8-11)。这两个位点的磷酸化会阻碍NEDD4L对ENaCs的抑制功能，并且通过其对Smad2/3的结合效应抑制了对TGF-β信号转导的调节功能(8-11)。

1. Kumar, S. et al. (1992) Biochem Biophys Res Commun 185, 1155-61.
2. Harvey, K.F. and Kumar, S. (1999) Trends Cell Biol 9, 166-9.
3. Dinudom, A. et al. (1998) Proc Natl Acad Sci USA 95, 7169-73.
4. Goulet, C.C. et al. (1998) J Biol Chem 273, 30012-7.
5. Staub, O. et al. (1996) EMBO J 15, 2371-80.
6. Kuratomi, G. et al. (2005) Biochem J 386, 461-70.
7. Harvey, K.F. et al. (1998) J Biol Chem 273, 13524-30.
8. Gao, S. et al. (2009) Mol Cell 36, 457-68.
9. Lee, I.H. et al. (2007) J Biol Chem 282, 29866-73.
10. Snyder, P.M. et al. (2004) J Biol Chem 279, 45753-8.
11. Debonneville, C. et al. (2001) EMBO J 20, 7052-9.

原厂资料：

Specificity / Sensitivity

Phospho-NEDD4L (Ser342) (D16D6) Rabbit mAb recognizes endogenous levels of NEDD4L protein only when phosphorylated at Ser342.

Source / Purification

Monoclonal antibody is produced by immunizing animals with a synthetic phosphopeptide corresponding to residues surrounding Ser342 of human NEDD4L protein.

Background

Neural precursor expressed, developmentally down-regulated protein 4 (NEDD4) was originally identified as a gene that is highly expressed in the early mouse embryonic central nervous system (1). Subsequently, a family of NEDD4-like proteins have been defined that includes seven members in humans (2). NEDD4 and NEDD4-like (NEDD4L) proteins contain multiple functional domains including a calcium-dependent phospholipid and membrane binding domain (C2 domain), two to four protein binding domains (WW domains), and an E3 ubiquitin-protein ligase domain (HECT domain). NEDD4 and NEDD4L have been shown to downregulate both neuronal voltage-gated Na+ channels (NaVs) and epithelial Na+ channels (ENaCs) in response to increased intracellular Na+ concentrations (3,4). The WW domains of NEDD4 bind to PY motifs (amino acid sequence PPXY) found in multiple NaV and ENaC proteins; ubiquitination of these proteins is mediated by the HECT domain of NEDD4 and results in their internalization and removal from the plasma membrane. Research studies have shown that mutation of the PY motifs in ENaC proteins is associated with Liddle's syndrome, an autosomal dominant form of hypertension (5). In addition to targeting sodium channels, NEDD4L has also been shown to negatively regulate TGF-β signaling by targeting Smad2 for degradation (6). Mouse and human NEDD4 are rapidly cleaved by caspase proteins during apoptosis, although the significance of this cleavage is not clear (7).

NEDD4L can be phosphorylated at Ser342 and Ser448 by several AGC kinase family members including SGK1, Akt, and PKA (8-11). Phosphorylation at these sites inhibits NEDD4L function as a suppressor of ENaCs and as a regulator of TGF-β signaling through its effects on Smad2/3 binding (8-11).

1. Kumar, S. et al. (1992) Biochem Biophys Res Commun 185, 1155-61.
2. Harvey, K.F. and Kumar, S. (1999) Trends Cell Biol 9, 166-9.
3. Dinudom, A. et al. (1998) Proc Natl Acad Sci USA 95, 7169-73.
4. Goulet, C.C. et al. (1998) J Biol Chem 273, 30012-7.
5. Staub, O. et al. (1996) EMBO J 15, 2371-80.
6. Kuratomi, G. et al. (2005) Biochem J 386, 461-70.
7. Harvey, K.F. et al. (1998) J Biol Chem 273, 13524-30.
8. Gao, S. et al. (2009) Mol Cell 36, 457-68.
9. Lee, I.H. et al. (2007) J Biol Chem 282, 29866-73.
10. Snyder, P.M. et al. (2004) J Biol Chem 279, 45753-8.
11. Debonneville, C. et al. (2001) EMBO J 20, 7052-9.

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