Phospho-Bim (Ser69) (D7E11) Rabbit mAb

• 产品编号：CST-4585S      品牌：CST       原厂货号：4585S
• 产品分类：抗体 > 一抗 > 磷酸化抗体
• 应用分类：

描述：

Phospho-Bim (Ser69) (D7E11) Rabbit mAb 兔单抗只能检测内源水平的Ser69位点磷酸化的Bim蛋白。该单克隆抗体是采用合成人Bim 蛋白Ser69 位点周围残基相对应的肽段来免疫动物而获得。Bim/Bod是促凋亡蛋白，属于Bcl-2家族只含有BH3域的成员，此家族还包括Bad、Bid、Bik、Hrk和 Noxa，它们都只包含BH3域，但缺少其它保守的BH1或BH2(1,2)。Bim通过结合并拮抗 Bcl-2家族抗凋亡因子而诱导凋亡。研究发现，其与Bcl-2、Bcl-xL、Mcl-1、Bcl-w、Bfl-1和 BHRF-1存在相互作用 (1,2)。Bim调控凋亡的功能是与胸腺细胞负向选择性有关，并伴随生长因子的撤回，在这期间Bim的表达是上调的(3-6)。Bim通过可变剪切，主要形成三种不同的形式：BimEL、BimL和BimS (1)。BimS是最短的形式，也是毒性最强的，它只在凋亡的瞬间表达。在凋亡过程中，BimEL 和 BimL 形式可能通过与动力蛋白的轻链互作，进而与动力蛋白复合体隔离并从这个复合体上得到释放(7)。这些长剪切形式的凋亡活性是通过磷酸化调控(8,9)。环境的胁迫引起JNK对Bim的磷酸化，并导致其与动力蛋白复合体的解离，从而增加凋亡活性。在生长因子的刺激下，BimEL依赖Erk1/2在Ser69位点(在小鼠和大鼠中是Ser65)磷酸化，能促够进蛋白酶体介导的降解并增强细胞的存活(6,10,11)。

1. O'Connor, L. et al. (1998) EMBO J 17, 384-95.
2. Hsu, S.Y. et al. (1998) Mol Endocrinol 12, 1432-40.
3. Bouillet, P. et al. (2002) Nature 415, 922-6.
4. Whitfield, J. et al. (2001) Neuron 29, 629-43.
5. Dijkers, P.F. et al. (2000) Curr Biol 10, 1201-4.
6. Ley, R. et al. (2003) J Biol Chem 278, 18811-6.
7. Puthalakath, H. et al. (1999) Mol Cell 3, 287-96.
8. Lei, K. and Davis, R.J. (2003) Proc Natl Acad Sci U S A 100, 2432-7.
9. Putcha, G.V. et al. (2003) Neuron 38, 899-914.
10. Luciano, F. et al. (2003) Oncogene 22, 6785-93.
11. Marani, M. et al. (2004) Oncogene 23, 2431-41.

原厂资料：

Homology

Species predicted to react based on 100% sequence homology: Rat, Monkey, Dog

Specificity / Sensitivity

Phospho-Bim (Ser69) (D7E11) Rabbit mAb detects endogenous levels of Bim protein only when phosphorylated at Ser69.

Source / Purification

Monoclonal antibody is produced by immunizing animals with a synthetic phosphopeptide corresponding to residues surrounding Ser69 of human Bim protein.

Background

Bim/Bod is a pro-apoptotic protein belonging to the BH3-only group of Bcl-2 family members including Bad, Bid, Bik, Hrk and Noxa that contain a BH3 domain but lack other conserved BH1 or BH2 domains (1,2). Bim induces apoptosis by binding to and antagonizing anti-apoptotic members of the Bcl-2 family. Interactions have been observed with Bcl-2, Bcl-xL, Mcl-1, Bcl-w, Bfl-1 and BHRF-1 (1,2). Bim functions in regulating apoptosis associated with thymocyte negative selection and following growth factor withdrawal, during which Bim expression is elevated (3-6). Three major isoforms of Bim are generated by alternative splicing: BimEL, BimL and BimS (1). The shortest form, BimS, is the most cytotoxic and is generally only transiently expressed during apoptosis. The BimEL and BimL isoforms may be sequestered to the dynein motor complex through an interaction with the dynein light chain and released from this complex during apoptosis (7). Apoptotic activity of these longer isoforms may be regulated by phosphorylation (8,9). Environmental stress triggers Bim phosphorylation by JNK and results in its dissociation from the dynein complex and increased apoptotic activity.ERK 1/2-dependent phosphorylation of BimEL at Ser69 (Ser65 in mouse and rat) in response to growth factor stimulation can promote its proteasome-mediated degradation and enhance cell survival (6,10,11).

1. O'Connor, L. et al. (1998) EMBO J 17, 384-95.
2. Hsu, S.Y. et al. (1998) Mol Endocrinol 12, 1432-40.
3. Bouillet, P. et al. (2002) Nature 415, 922-6.
4. Whitfield, J. et al. (2001) Neuron 29, 629-43.
5. Dijkers, P.F. et al. (2000) Curr Biol 10, 1201-4.
6. Ley, R. et al. (2003) J Biol Chem 278, 18811-6.
7. Puthalakath, H. et al. (1999) Mol Cell 3, 287-96.
8. Lei, K. and Davis, R.J. (2003) Proc Natl Acad Sci U S A 100, 2432-7.
9. Putcha, G.V. et al. (2003) Neuron 38, 899-914.
10. Luciano, F. et al. (2003) Oncogene 22, 6785-93.
11. Marani, M. et al. (2004) Oncogene 23, 2431-41.

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.