Phospho-Bim (Ser55) Antibody

• 产品编号：CST-4550S      品牌：CST       原厂货号：4550S
• 产品分类：抗体 > 一抗 > 磷酸化抗体
• 应用分类：

描述：

Phospho-Bim (Ser55) Antibody 只能检测小鼠源的Ser55位点磷酸化的Bim蛋白。此位点在大鼠(Ser55) 和人(Ser59)中是保守的，但是在这些物种中却没有磷酸化。多克隆抗体是采用合成小鼠Bim Ser55位点周围残基相对应的磷酸化肽段来免疫动物而获得。抗体是通过protein A和多肽亲和层析法纯化。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。存活因子诱导ERK的激活，导致了小鼠Bim在Ser55位点的磷酸化，这就抑制了它的促凋亡活性及与Bax的联合(10)。

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. Harada, H. et al. (2004) Proc Natl Acad Sci USA 101, 15313-15317.

原厂资料：

Homology

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

Specificity / Sensitivity

Phospho-Bim (Ser55) Antibody detects endogenous levels of mouse Bim protein only when phosphorylated at Ser55. This site is conserved in rat (Ser55) and human (Ser59) but phosphorylation has not been detected in these species.

Source / Purification

Polyclonal antibodies are produced by immunizing animals with a synthetic phosphopeptide corresponding to residues surrounding Ser55 of mouse Bim. Antibodies were purified by protein A and peptide affinity chromatography.

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.Survival factor induced ERK activation leads to phosphorylation of mouse Bim at Ser55, which inhibits its pro-apoptotic activity and association with Bax (10).

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. Harada, H. et al. (2004) Proc Natl Acad Sci USA 101, 15313-15317.

注意事项：

Storage: Supplied in 10 mM sodium HEPES (pH 7.5), 150 mM
NaCl, 100 µg/ml BSA and 50% glycerol. Store at –20°C.
Do not aliquot the antibody