Cleaved Notch1 (Val1744) (D3B8) Rabbit mAb

• 产品编号：CST-4147P      品牌：Cell Signaling Technology       原厂货号：4147P
• 产品分类：抗体 > 一抗 > 蛋白特异性一抗
• 应用分类：

描述：

剪切的Notch1 (Val1744) (D3B8)Rabbit mAb兔单抗只识别甘氨酸1743和缬氨酸1744倍剪切的内源性Notch1 蛋白的胞质结构域。此抗体不识别全长Notch1或Notch1其他位置剪切型Notch1。不同细胞系会存在Notch1远端羧基末端的突变，因此导致抗体检测不同大小的剪切型Notch1（见参考文献6和7）.单克隆抗体是通过一种合成的肽段去免疫动物产生。这种合成的肽段与邻近人源Notch1蛋白的Val1744剪切点的氨基酸残基序列一致。Notch1是一个在细胞发育和命运决定过程中发挥功能的跨膜蛋白（1）。在notch1成熟过程中，notch1分子细胞外结构域会被一个成对碱性氨基酸蛋白酶样的转化酶剪切（2）。在与配体如Delta1结合或是细胞外钙离子耗竭后，notch1的羧基端被释放并随后在Gly1743 和 Val1744之间被切开（3,4）。结果导致细胞内处于活化状态的notch1片段转运至细胞核内并转录激活。组成型激活Notch1信号通路与T细胞急性淋巴母细胞白血病（T-ALL）的主因有关，Notch1信号通路的活化与Notch1自身突变或泛素连接酶组件FBW7有关（5-7）.

1. Artavanis-Tsakonas, S. et al. (1999) Science 284, 770-6.
2. Chan, Y.M. and Jan, Y.N. (1998) Cell 94, 423-6.
3. Schroeter, E.H. et al. (1998) Nature 393, 382-6.
4. Rand, M.D. et al. (2000) Mol Cell Biol 20, 1825-35.
5. Weng, A.P. et al. (2004) Science 306, 269-71.
6. Thompson, B.J. et al. (2007) J Exp Med 204, 1825-35.

原厂资料：

Specificity / Sensitivity

Cleaved Notch1 (Val1744) (D3B8) Rabbit mAb detects endogenous levels of the cytosolic domain of Notch1 only when cleaved between Gly1743 and Val1744. The antibody does not recognize full length Notch1 or Notch1 cleaved at other positions. It detects Cleaved Notch1 with different sizes in different cell lines due to mutations at the distant C-termini of Notch1 (see refs 6 and 7).

Source / Purification

Monoclonal antibody is produced by immunizing animals with a synthetic peptide corresponding to the sequence at the Val1744 cleavage site of human Notch1.

Background

Notch1 is a transmembrane protein functioning in development and the determination of cell fate (1). During maturation, the notch molecule is cleaved by a furin-like convertase at its extracellular domain (2). Upon binding to a ligand such as Delta1, or upon extracellular calcium depletion, the carboxy-terminal notch1 fragment is released and further cleaved between Gly1743 and Val1744 (3,4). The resulting activated cytosolic fragment translocates to the nucleus where it activates transcription.Constitutively activated Notch1 signaling is associated with the majority of cases of T cell acute lymphoblastic leukemia (T-ALL). The activation is either due to mutations in Notch1 itself or in the components of ubiquitin ligase complex, namely FBW7 (5-7).

1. Artavanis-Tsakonas, S. et al. (1999) Science 284, 770-6.
2. Chan, Y.M. and Jan, Y.N. (1998) Cell 94, 423-6.
3. Schroeter, E.H. et al. (1998) Nature 393, 382-6.
4. Rand, M.D. et al. (2000) Mol Cell Biol 20, 1825-35.
5. Weng, A.P. et al. (2004) Science 306, 269-71.
6. Thompson, B.J. et al. (2007) J Exp Med 204, 1825-35.

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