PKM2 (D78A4) XP? Rabbit mAb?(Sepharose? Bead Conjugate)

• 产品编号：CST-13266S      品牌：CST       原厂货号：13266S
• 产品分类：抗体 > 一抗 > 其它类型一抗
• 应用分类：

描述：

PKM2 (D78A4) XP® Rabbit mAb兔单抗 (Sepharose® Bead Conjugate)可以检测到内源性PKM2总蛋白水平。单克隆抗体由合成肽段免疫动物产生，该肽段与人PKM2蛋白氨基酸序列一致。Cell Signaling Technology 抗体通过氨基酸上的共价伯氨基与N-hydroxysuccinimide (NHS)-activated sepharose ®珠固定。PKM2 (D78A4) XP®Rabbit mAb 兔单抗 (Sepharose®Bead Conjugate)用于免疫沉淀PKM2。该抗体与没有偶联的PKM2 (D78A4) XP®Rabbit mAb #4053具有相同的交叉反应性。丙酮酸激酶，是糖酵解过程中的酶，负责将磷酸烯醇式丙酮酸转化为丙酮酸。在哺乳动物中，M1同工酶PKM1在大多数成年组织中都有表达（1）。而M2同工酶PKM2作为M1的一种可变剪切形式，在胚胎发育过程中表达（1）。研究表明肿瘤细胞中只表达PKM2（1－3）。PKM2在肿瘤细胞中可能对无氧糖酵解是必需的（即warburg效应）（1）。当将M2转变成M1形式后，肿瘤细胞中的无氧糖酵解反应减弱，而氧化磷酸化增强（1）。这样的细胞同时在小鼠身上的成瘤能力也降低（1）。最近的研究表达，原癌基因FGFR1会直接磷酸化PKM2的Tyr105，从而抑制PKM2形成四聚体的活性形式（4）。在肿瘤细胞中发现了一种PKM2的突变形式，它的Tyr105被苯丙氨酸替代，会导致裸鼠细胞低氧条件下细胞增殖和肿瘤生长减慢（4）。这些研究都表明，Tyr105的磷酸化转变是肿瘤细胞快速增长的一个关键机制（4）。

1. Christofk, H.R. et al. (2008) Nature 452, 230-3.
2. Mazurek, S. et al. (2005) Semin Cancer Biol 15, 300-8.
3. Dombrauckas, J.D. et al. (2005) Biochemistry 44, 9417-29.
4. Israelsen, W.J. et al. (2013) Cell 155, 397-409.

原厂资料：

Specificity / Sensitivity

PKM2 (D78A4) XP^® Rabbit mAb (Sepharose^® Bead Conjugate) detects endogenous levels of total PKM2 protein.

Source / Purification

Monoclonal antibody is produced by immunizing animals with a synthetic peptide corresponding to the sequence of human PKM2 protein.

Description

This Cell Signaling Technology antibody is immobilized via covalent binding of primary amino groups to N-hydroxysuccinimide (NHS)-activated sepharose^® beads. PKM2 (D78A4) XP^® Rabbit mAb (Sepharose^® Bead Conjugate) is useful for the immunoprecipitation of PKM2. The antibody is expected to exhibit the same species cross-reactivity as the unconjugated PKM2 (D78A4) XP^® Rabbit mAb #4053.

Background

Pyruvate kinase is a glycolytic enzyme that catalyses the conversion of phosphoenolpyruvate to pyruvate. In mammals, the M1 isoform (PKM1) is expressed in most adult tissues (1). The M2 isoform (PKM2) is an alternatively spliced variant of M1 that is expressed during embryonic development (1). Research studies found that cancer cells exclusively express PKM2 (1-3). PKM2 is shown to be essential for aerobic glycolysis in tumors, known as the Warburg effect (1). When cancer cells switch from the M2 isoform to the M1 isoform, aerobic glycolysis is reduced and oxidative phosphorylation is increased (1). These cells also show decreased tumorigenicity in mouse xenografts (1). Additional studies show that the oncogenic forms of FGFR1 directly phosphorylate Tyr105 of PKM2 and thereby inhibit the formation of active, tetrameric PKM2 (4). A PKM2 missense mutation found in cancer cells results in the replacement of Tyr105 by phenylalanine and leads to reduced cell proliferation during hypoxia and tumor growth in nude mice xenografts (4). These findings suggest that the phosphorylation at Tyr105 is a critical switch for the metabolism in cancer cells that promotes tumor growth (4).

1. Christofk, H.R. et al. (2008) Nature 452, 230-3.
2. Mazurek, S. et al. (2005) Semin Cancer Biol 15, 300-8.
3. Dombrauckas, J.D. et al. (2005) Biochemistry 44, 9417-29.
4. Israelsen, W.J. et al. (2013) Cell 155, 397-409.

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.