SignalSilence? HER3/ErbB3 siRNA II

• 产品编号：CST-6422S      品牌：CST       原厂货号：6422S
• 产品分类：DNA和RNA纯化 > RNA干扰 > RNAi Oligos > siRNA
• 应用分类：

描述：

CST公司的SignalSilence® HER3/ErbB3 siRNA II能够通过RNA干扰的方法特异阻断HER3/ErbB3的表达，本方法通过向细胞内输入双链RNA选择性地对基因表达进行沉默。所有的SignalSilence® siRNA产品均经过严格的内部测试并在免疫印迹检测中显示能够降低靶蛋白的表达。通过三苯甲基分析每个碱基以监测寡核苷酸的合成，确保合适的配对效率。随后寡核苷酸通过亲和固相萃取法纯化。退火的RNA双链通过质谱分析来证实其精确的组成。每一批产品都通过质谱分析与前面的产品进行比较，来保证不同批次之间的最大一致性。CST建议使用100 nM HER3/ErbB3 siRNA II 转染48-72小时后裂解细胞。转染的具体步骤请参考转染试剂制造商提供的操作标准。使用过程中有任何问题请随时联系CST。HER3/ErbB3是ErbB酪氨酸激酶受体蛋白家族的成员之一，但却没有酪氨酸激酶活性。ErbB3的酪氨酸位点磷酸化依赖于其它ErbB酪氨酸激酶。与配体结合后，ErbB3与其它ErbB蛋白形成异二聚体,并且其酪氨酸位点能够被激活的ErbB激酶磷酸化（1，2）。在ErbB3的羧基端至少有9个潜在的酪氨酸磷酸化位点。这些位点都是信号转导蛋白一致的结合位点，这些蛋白包括Src家族的分子，Grb2, 和PI3K激酶的p85亚基，它们都能参与ErbB的下游信号调节(3)。ErbB3 的Tyr1222和Tyr1289残基都位于一个YXXM基序上并参与PI3K激酶的信号传递(4)。ErbB3高表达于很多癌细胞中（5），而ErbB3/PI3K通路的激活也和许多腺癌的恶性特征相关（6）。在肿瘤发展过程中，ErbB3可能和ErbB家族的其它成员（如，ErbB2需要和ErbB3一起促进乳腺癌细胞的增殖）作为一个原癌基因单位一起发挥功能（7）。因此，抑制ErbB3和ErbB酪氨酸激酶的相互作用已经成为抗癌治疗中的一个新策略。

1. Yarden, Y. and Sliwkowski, M.X. (2001) Nat Rev Mol Cell Biol 2, 127-37.
2. Guy, P.M. et al. (1994) Proc Natl Acad Sci U S A 91, 8132-6.
3. Songyang, Z. et al. (1993) Cell 72, 767-78.
4. Kim, H.H. et al. (1994) J Biol Chem 269, 24747-55.
5. Sithanandam, G. et al. (2003) Carcinogenesis 24, 1581-92.
6. Kobayashi, M. et al. (2003) Oncogene 22, 1294-301.
7. Holbro, T. et al. (2003) Proc Natl Acad Sci U S A 100, 8933-8.

原厂资料：

Description

SignalSilence® HER3/ErbB3 siRNA II from Cell Signaling Technology (CST) allows the researcher to specifically inhibit HER3/ErbB3 expression using RNA interference, a method whereby gene expression can be selectively silenced through the delivery of double stranded RNA molecules into the cell. All SignalSilence® siRNA products from CST are rigorously tested in-house and have been shown to reduce target protein expression by western analysis.

Quality Control

Oligonucleotide synthesis is monitored base by base through trityl analysis to ensure appropriate coupling efficiency. The oligo is subsequently purified by affinity-solid phase extraction. The annealed RNA duplex is further analyzed by mass spectrometry to verify the exact composition of the duplex. Each lot is compared to the previous lot by mass spectrometry to ensure maximum lot-to-lot consistency.

Directions for Use

CST recommends transfection with 100 nM HER3/ErbB3 siRNA II 48 to 72 hours prior to cell lysis. For transfection procedure, follow protocol provided by the transfection reagent manufacturer. Please feel free to contact CST with any questions on use.

Background

HER3/ErbB3 is a member of the ErbB receptor protein tyrosine kinase family, but lacks tyrosine kinase activity. Tyrosine phosphorylation of ErbB3 depends on its association with other ErbB tyrosine kinases. Upon ligand binding, heterodimers form between ErbB3 and other ErbB proteins and ErbB3 is phosphorylated on tyrosine residues by the activated ErbB kinase (1,2). There are at least 9 potential tyrosine phosphorylation sites in the carboxy-terminal tail of ErbB3. These sites serve as consensus binding sites for signal transducing proteins, including Src family members, Grb2, and the p85 subunit of PI3 kinase, which mediate ErbB downstream signaling (3). Both Tyr1222 and Tyr1289 of ErbB3 reside within a YXXM motif and participate in signaling to PI3 kinase (4). 
 ErbB3 is highly expressed in many cancer cells (5) and activation of the ErbB3/PI3K pathway is correlated with malignant phenotypes of adenocarcinomas (6). In tumor development, ErbB3 may function as an oncogenic unit together with other ErbB members (e.g. ErbB2 requires ErbB3 to drive breast tumor cell proliferation) (7). Thus, inhibiting interaction between ErbB3 and ErbB tyrosine kinases has become a novel strategy for anti-tumor therapy.

1. Yarden, Y. and Sliwkowski, M.X. (2001) Nat Rev Mol Cell Biol 2, 127-37.
2. Guy, P.M. et al. (1994) Proc Natl Acad Sci U S A 91, 8132-6.
3. Songyang, Z. et al. (1993) Cell 72, 767-78.
4. Kim, H.H. et al. (1994) J Biol Chem 269, 24747-55.
5. Sithanandam, G. et al. (2003) Carcinogenesis 24, 1581-92.
6. Kobayashi, M. et al. (2003) Oncogene 22, 1294-301.
7. Holbro, T. et al. (2003) Proc Natl Acad Sci U S A 100, 8933-8.

注意事项：

Storage: SignalSilence® siRNA is supplied in RNAse-free water. Aliquot and store at -20ºC.