Notch3 (D11B8) Rabbit mAb

• 产品编号：CST-5276P      品牌：Cell Signaling Technology       原厂货号：5276P
• 产品分类：抗体 > 一抗 > 蛋白特异性一抗
• 应用分类：

描述：

Notch3 (D11B8)Rabbit mAb识别内源性的总Notch3蛋白。此抗体可以识别Notch3的270 kDa的全长蛋白（FL）和90 kDa的截短蛋白（NTM），这个截短蛋白包含一个短的胞外结构，跨膜区域和胞内区域。合成与人Notch3蛋白邻近Glu2312氨基酸残基序列一致的肽段，免疫动物获得单克隆抗体。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。Notch3是Notch家族的成员之一，与Notch1的形成类似（5）。它主要在动脉平滑肌细胞中表达（SMC）。Notch3细胞外区域半胱氨酸残基数目改变导致的突变与大脑常染色体显性动脉病合并皮层下梗塞及脑白质病（CADASIL）有关，是一种遗传性的血管疾病，会导致中风和成年人痴呆（6-8）。最近的研究显示Notch3在多种癌症中表达上调（9-11）。

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. Baron, M. (2003) Semin Cell Dev Biol 14, 113-9.
6. Kalimo, H. et al. (2002) Brain Pathol 12, 371-84.
7. Karlström, H. et al. (2002) Proc Natl Acad Sci U S A 99, 17119-24.
8. Monet, M. et al. (2007) Hum Mol Genet 16, 982-92.
9. Park, J.T. et al. (2006) Cancer Res 66, 6312-8.
10. Gramantieri, L. et al. (2007) Liver Int 27, 997-1007.
11. Yamaguchi, N. et al. (2008) Cancer Res 68, 1881-8.

原厂资料：

Specificity / Sensitivity

Notch3 (D11B8) Rabbit mAb detects endogenous levels of total Notch3 protein. The antibody recognizes both full-length (FL) Notch3 at 270 kDa and a truncated protein (NTM) containing a short extracellular region, the transmembrane domain and the intracellular region at 90 kDa.

Source / Purification

Monoclonal antibody is produced by immunizing animals with a synthetic peptide corresponding to residues surrounding Glu2312 of human Notch3 protein.

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.Notch3 is a member of the Notch family and is processed similar to Notch1 (5). It is expressed primarily in arterial smooth muscle cells (SMC). Mutations altering the number of cysteine residues in the Notch3 extracellular region are associated with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), a hereditary angiopathy leading to strokes and dementia in adults (6-8). Recent studies indicate that Notch3 is overexpressed in many types of cancer (9-11).

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. Baron, M. (2003) Semin Cell Dev Biol 14, 113-9.
6. Kalimo, H. et al. (2002) Brain Pathol 12, 371-84.
7. Karlström, H. et al. (2002) Proc Natl Acad Sci U S A 99, 17119-24.
8. Monet, M. et al. (2007) Hum Mol Genet 16, 982-92.
9. Park, J.T. et al. (2006) Cancer Res 66, 6312-8.
10. Gramantieri, L. et al. (2007) Liver Int 27, 997-1007.
11. Yamaguchi, N. et al. (2008) Cancer Res 68, 1881-8.

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.