Phospho-SHIP2 (Tyr1135) (D33C6) XP? Rabbit mAb

• 产品编号：CST-5445S      品牌：CST       原厂货号：5445S
• 产品分类：抗体 > 一抗 > 磷酸化抗体
• 应用分类：

描述：

Phospho-SHIP2 (Tyr1135) (D33C6) XP® Rabbit mAb兔多抗能检测内源性酪氨酸（1135位点）磷酸化的SHIP2蛋白水平。该单克隆抗体通过使用与人源SHIP2蛋白酪氨酸（1135位点）周围残基相一致的合成磷酸化肽段免疫动物而获得。该抗体经蛋白A和肽亲和层析纯化。含有SH2结构域的肌糖磷酸酶1(SHIP1)是一种造血磷酸酶，该酶能水解phosphatidylinositol-3,4,5-triphosphate，产生phosphatidylinositol-3,4-bisphosphate (1)。SHIP1是一种催化性酶，它的胺端有SH2结构域，羧端有两个NPXY Shc结合基序(1,2)。依靠受体的交联，SHIP通过SH2结构域与ITIM基序的磷酸化酪氨酸的结合，第一个被聚集到胞膜连接处，接着是NPXY基序的酪氨酸被磷酸化(2)。NPXY基序在膜上的重新定位以及磷酸化对于SHIP1的调节性功能十分重要(3-5)。它对钙流动、细胞生存、、生长、细胞周期捕获和凋亡效应的调节通过PI3K、Akt 途径实现(3-5)。酪氨酸1021位点定位于NPXY基序的SHIP1中，它的磷酸化对SHIP1的功能很重要(6)。SHIP2是 SHIP1的同源物，它高表达于心脏、骨骼肌和胎盘内(7)。SHIP2负调节胰岛素的信号传递(8) ，并且SHIP2的多态性与高血糖症有关 (9)。最近的研究也暗示SHIP2是肥胖症和2型糖尿病治疗的靶点(10,11)。人癌细胞中酪氨酸1135位点被磷酸化(12-15)。

1. Tridandapani, S. et al. (1997) Mol Cell Biol 17, 4305-11.
2. Liu, L. et al. (1997) J Biol Chem 272, 8983-8.
3. Malbec, O. et al. (2001) J Biol Chem 276, 30381-91.
4. Carver, D.J. et al. (2000) Blood 96, 1449-56.
5. Scharenberg, A.M. et al. (1998) EMBO J 17, 1961-72.
6. Sattler, M. et al. (2001) J Biol Chem 276, 2451-8.
7. Pesesse, X. et al. (1997) Biochem Biophys Res Commun 239, 697-700.
8. Wada, T. et al. (2001) Mol Cell Biol 21, 1633-46.
9. Ishida, S. et al. (2006) Pancreas 33, 63-7.
10. Dyson, J.M. et al. (2005) Int J Biochem Cell Biol 37, 2260-5.
11. Liang, X. et al. (2006) Proteomics 6, 4554-64.
12. Goss, V.L. et al. (2006) Blood 107, 4888-97.
13. Guo, A. et al. (2008) Proc Natl Acad Sci U S A 105, 692-7.
14. Rikova, K. et al. (2007) Cell 131, 1190-203.

原厂资料：

Specificity / Sensitivity

Phospho-SHIP2 (Tyr1135) (D33C6) XP® Rabbit mAb detects endogenous levels of SHIP2 protein only when phosphorylated at Tyr1135.

Source / Purification

Monoclonal antibody is produced by immunizing animals with a synthetic phosphopeptide corresponding to residues surrounding Tyr1135 of human SHIP2 protein.

Background

SH2-containing inositol phosphatase 1 (SHIP1) is a hematopoietic phosphatase that hydrolyzes phosphatidylinositol-3,4,5-triphosphate to phosphatidylinositol-3,4-bisphosphate (1). SHIP1 is a cytosolic phosphatase with an SH2 domain in its amino terminus and two NPXY Shc binding motifs in its carboxy terminus (1,2). Upon receptor cross-linking, SHIP is first recruited to the membrane junction through binding of its SH2 domain to the phospho-tyrosine in the ITIM motif (2), followed by tyrosine phosphorylation on the NPXY motif (2). The membrane relocalization and phosphorylation on the NPXY motif is essential for the regulatory function of SHIP1 (3-5). Its effect on calcium flux, cell survival, growth, cell cycle arrest and apoptosis is mediated through the PI3K and Akt pathways (3-5). Tyr1021 is located in one of the NPXY motifs in SHIP1, and its phosphorylation is important for SHIP1 function (6).SHIP2, a homolog of SHIP1, is highly expressed in heart, skeletal muscle and placenta (7). SHIP2 negatively regulates insulin signaling (8) and polymorphisms in SHIP2 have been linked to hyperglycemia (9). Recent studies also suggest SHIP2 as a therapeutic target for the treatment of both obesity and type 2 diabetes (10,11). Tyr1135 is phosphorylated in human cancer cells (12-15).

1. Tridandapani, S. et al. (1997) Mol Cell Biol 17, 4305-11.
2. Liu, L. et al. (1997) J Biol Chem 272, 8983-8.
3. Malbec, O. et al. (2001) J Biol Chem 276, 30381-91.
4. Carver, D.J. et al. (2000) Blood 96, 1449-56.
5. Scharenberg, A.M. et al. (1998) EMBO J 17, 1961-72.
6. Sattler, M. et al. (2001) J Biol Chem 276, 2451-8.
7. Pesesse, X. et al. (1997) Biochem Biophys Res Commun 239, 697-700.
8. Wada, T. et al. (2001) Mol Cell Biol 21, 1633-46.
9. Ishida, S. et al. (2006) Pancreas 33, 63-7.
10. Dyson, J.M. et al. (2005) Int J Biochem Cell Biol 37, 2260-5.
11. Liang, X. et al. (2006) Proteomics 6, 4554-64.
12. Goss, V.L. et al. (2006) Blood 107, 4888-97.
13. Guo, A. et al. (2008) Proc Natl Acad Sci U S A 105, 692-7.
14. Rikova, K. et al. (2007) Cell 131, 1190-203.

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