APPL1 (D83H4) XP? Rabbit mAb

• 产品编号：CST-3858P      品牌：Cell Signaling Technology       原厂货号：3858P
• 产品分类：抗体 > 一抗 > 蛋白特异性一抗
• 应用分类：

描述：

APPL1 (D83H4) XP®Rabbit mAb兔单抗识别内源性的全部APPL1蛋白。该单克隆抗体用与人类APPL1蛋白中Thr426位点附近的氨基酸序列对应的人工合成肽段免疫动物而制成。APPL1多结构域接头蛋白是一个BAR结构域蛋白家族成员，参与一系列信号转导途径和膜转运（7）。氨基末端的BAR结构域介导月牙形APPL1同源二聚体（或APPL1和APPL2异源二聚体）形成，对脂肪结合和膜曲率传感非常重要（1）。APPL1的PH结构域用于与接头蛋白Rab5 GTP酶结合（2）。在对细胞外刺激的反应中，Rab5 GTP从内体中水解释放APPL1，使其可转位到细胞核组成蛋白复合物，控制染色质重塑和基因表达（3）。APPL1羧基末端的PTB结构域使得APPL1可以与TrkA神经营养因子受体相互作用。内体中这两种蛋白以及TrkA互作蛋白GIPC1的相互作用为神经生长因子介导信号通路所需（4）。APPL1也能结合促卵泡激素（FSH）受体，传递FSH信号到PI3K/Akt通路（5）。APPL1接头蛋白与胰岛素信号有关，APPL1和Akt2相互作用为胰岛素刺激的GLUT4受体转位所需。APPL1的过表达或下调都会抑制胰岛素刺激的GLUT4转位（6）。APPL1结合脂联素受体，作为脂联素受体信号通路下游效应物介导一氧化碳生成（7，8）。APPL1与DCC（大肠癌中缺失）蛋白相互作用，在DCC诱导的凋亡中扮演作用（9）。

1. Habermann, B. (2004) EMBO Rep 5, 250-5.
2. Zhu, G. et al. (2007) EMBO J 26, 3484-93.
3. Miaczynska, M. et al. (2004) Cell 116, 445-56.
4. Lin, D.C. et al. (2006) Mol Cell Biol 26, 8928-41.
5. Nechamen, C.A. et al. (2004) Biol Reprod 71, 629-36.
6. Saito, T. et al. (2007) J Biol Chem 282, 32280-7.
7. Mao, X. et al. (2006) Nat Cell Biol 8, 516-23.
8. Cheng, K.K. et al. (2007) Diabetes 56, 1387-94.
9. Liu, J. et al. (2002) J Biol Chem 277, 26281-5.
10. Hennig, J. et al. (2014) Cell Death Dis 5, e1199.

原厂资料：

Specificity / Sensitivity

APPL1 (D83H4) XP® Rabbit mAb detects endogenous levels of total APPL1 protein.

Source / Purification

Monoclonal antibody is produced by immunizing animals with a synthetic peptide corresponding to residues surrounding Thr426 of human APPL1.

Background

The APPL1 multidomain adaptor protein is a BAR-domain protein family member that is involved in membrane trafficking within a number of signal transduction pathways (1). The amino-terminal BAR domain mediates the formation of crescent-shaped APPL1 homodimers (or APPL1 and APPL2 heterodimers) important to lipid binding and membrane curvature sensing (1). The PH domain of APPL1 is required for binding of the adaptor protein to Rab5 GTPase (2). In response to extracellular stimuli, Rab5 GTP hydrolysis releases APPL1 from the endosome and allows translocation of APPL1 to the nucleus where it joins a protein complex that controls chromatin remodeling and gene expression (3). The carboxy-terminal PTB domain of APPL1 enables an interaction between APPL1 and the TrkA neurotrophin receptor. An association between these two proteins and the TrkA-interacting protein GIPC1 within endosomes is required for nerve growth factor mediated signaling (4). APPL1 also binds follicle-stimulating hormone (FSH) receptors, which may provide a relay of FSH signaling to the PI3K/Akt pathway (5). The APPL1 adaptor protein is implicated in insulin signaling, as interaction between APPL1 and Akt2 is required for insulin-stimulated translocation of GLUT4 receptor proteins. Both induced overexpression and knockdown of APPL1 inhibit insulin-stimulated GLUT4 translocation (6). APPL1 binds the adiponectin receptor and acts as a downstream effector in the adiponectin pathway to mediate NO production (7,8). APPL1 interacts with DCC (deleted in colorectal cancer) protein and may play a role in DCC-induced apoptosis (9).

1. Habermann, B. (2004) EMBO Rep 5, 250-5.
2. Zhu, G. et al. (2007) EMBO J 26, 3484-93.
3. Miaczynska, M. et al. (2004) Cell 116, 445-56.
4. Lin, D.C. et al. (2006) Mol Cell Biol 26, 8928-41.
5. Nechamen, C.A. et al. (2004) Biol Reprod 71, 629-36.
6. Saito, T. et al. (2007) J Biol Chem 282, 32280-7.
7. Mao, X. et al. (2006) Nat Cell Biol 8, 516-23.
8. Cheng, K.K. et al. (2007) Diabetes 56, 1387-94.
9. Liu, J. et al. (2002) J Biol Chem 277, 26281-5.
10. Hennig, J. et al. (2014) Cell Death Dis 5, e1199.

注意事项：

Storage: Supplied in 10mM 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.