Phospho-Jak2 (Tyr1008) (D4A8) Rabbit mAb

• 产品编号：CST-8082S      品牌：CST       原厂货号：8082S
• 产品分类：抗体 > 一抗 > 磷酸化抗体
• 应用分类：

描述：

Phospho-Jak2 (Tyr1008) (D4A8) Rabbit mAb 只能检测内源的在Tyr1008位点磷酸化的Jak2 蛋白。此抗体也能识别在Tyr1007和Tyr1008位点双磷酸化的Jak2。此抗体经过western免疫印迹实验证明不与Jak2家族的其它成员交叉反应。单克隆抗体是通过合成人源对应的Jak2 Tyr1008位点周围的肽段来免疫动物而获得。Janus家族中的酪氨酸激酶成员(Jak1, Jak2, Jak3和Tyk2)通过配体结合到一些相关的细胞因子受体上而被激活（1）.除了细胞因子受体的激活方式，Jak蛋白能自身磷酸化和磷酸化与其相关的受体从而为信号蛋白提供多个结合位点。这些信号蛋白如Stats (2)、Shc (3)、胰岛素受体底物(4) 和成簇黏附激酶 (FAK) (5)都是典型的含有SH2 或者其它的磷-酪氨酸结合区域。ak2 信号通路与很多细胞因子的刺激有关，生长因子和激素有关包括IL-3, IL-5, IL-6, 粒细胞巨噬细胞集落刺激因子(GM-CSF), 促红细胞生成素(EPO), 血小板生成素(TPO) 生长激素，催乳素和瘦素(6-13)。潜在的致瘤性Jak2 现在已经被认识，尽管其易位和点突变导致它对激酶活性下调加强, 这促使Jak2是一个潜在的治疗靶点。在白血病病人中发现Jak2 基因的易位导致其与TEL (TEL-JAK2) 和 PCM1 (PCM1-JAK2)形成融合蛋(14,15)。在Jak2中激活为位点的突变导致在617位点缬氨酸转变成苯丙氨酸 (V617F) ，此现象在骨髓增生性疾病包括真性红细胞增多症、原发性血小板增多症中有发现(16)。

1. Leonard, W.J. and O'Shea, J.J. (1998) Annu Rev Immunol 16, 293-322.
2. Darnell, J.E. (1997) Science 277, 1630-5.
3. VanderKuur, J. et al. (1995) J Biol Chem 270, 7587-93.
4. Argetsinger, L.S. et al. (1995) J Biol Chem 270, 14685-92.
5. Zhu, T. et al. (1998) J Biol Chem 273, 10682-9.
6. Quelle, F.W. et al. (1994) Mol Cell Biol 14, 4335-41.
7. Witthuhn, B.A. et al. (1993) Cell 74, 227-36.
8. Tortolani, P.J. et al. (1995) Blood 85, 3444-51.
9. Pallard, C. et al. (1995) EMBO J 14, 2847-56.
10. Narazaki, M. et al. (1994) Proc Natl Acad Sci USA 91, 2285-9.
11. Argetsinger, L.S. et al. (1993) Cell 74, 237-44.
12. Rui, H. et al. (1994) J Biol Chem 269, 5364-8.
13. Ghilardi, N. and Skoda, R.C. (1997) Mol Endocrinol 11, 393-9.
14. Lacronique, V. et al. (1997) Science 278, 1309-12.
15. Reiter, A. et al. (2005) Cancer Res 65, 2662-7.
16. Kralovics, R. et al. (2005) N Engl J Med 352, 1779-90.

原厂资料：

Homology

Species predicted to react based on 100% sequence homology: Rat, Monkey, Xenopus, Bovine, Pig

Specificity / Sensitivity

Phospho-Jak2 (Tyr1008) (D4A8) Rabbit mAb recognizes endogenous levels of Jak2 protein only when phosphorylated at Tyr1008. This antibody also reacts with Jak2 when dually phosphorylated at Tyr1007 and Tyr1008. Cross-reactivity was not observed with other Jak family members by western blot.

Source / Purification

Monoclonal antibody is produced by immunizing animals with a synthetic peptide corresponding to residues surrounding Tyr1008 of human Jak2 protein.

Background

Members of the Janus family of tyrosine kinases (Jak1, Jak2, Jak3, and Tyk2) are activated by ligands binding to a number of associated cytokine receptors (1). Upon cytokine receptor activation, Jak proteins become autophosphorylated and phosphorylate their associated receptors to provide multiple binding sites for signaling proteins. These associated signaling proteins, such as Stats (2), Shc (3), insulin receptor substrates (4), and focal adhesion kinase (FAK) (5), typically contain SH2 or other phospho-tyrosine-binding domains.Jak2 signaling is associated with a number of cytokines, growth factors, and hormones including IL-3, IL-5, IL-6, granulocyte-macrophage colony-stimulating factor (GM-CSF), erythropoietin (EPO), thrombopoietin (TPO) growth hormone, prolactin, and leptin (6-13). The oncogenic potential of Jak2 has been realized though translocations and point mutations resulting in its enhanced, de-regualated kinase activity, making Jak2 a potential therapeutic target. Jak2 gene translocations resulting in fusions with the TEL (TEL-JAK2) and PCM1 (PCM1-JAK2) have been found in leukemia patients (14,15). An activating point mutation in Jak2 resulting in a valine to phenylalanine switch at position 617 (V617F) has been implicated in myeloproliferative disorders including polycythemia vera and essential thrombocythemia (16).

1. Leonard, W.J. and O'Shea, J.J. (1998) Annu Rev Immunol 16, 293-322.
2. Darnell, J.E. (1997) Science 277, 1630-5.
3. VanderKuur, J. et al. (1995) J Biol Chem 270, 7587-93.
4. Argetsinger, L.S. et al. (1995) J Biol Chem 270, 14685-92.
5. Zhu, T. et al. (1998) J Biol Chem 273, 10682-9.
6. Quelle, F.W. et al. (1994) Mol Cell Biol 14, 4335-41.
7. Witthuhn, B.A. et al. (1993) Cell 74, 227-36.
8. Tortolani, P.J. et al. (1995) Blood 85, 3444-51.
9. Pallard, C. et al. (1995) EMBO J 14, 2847-56.
10. Narazaki, M. et al. (1994) Proc Natl Acad Sci USA 91, 2285-9.
11. Argetsinger, L.S. et al. (1993) Cell 74, 237-44.
12. Rui, H. et al. (1994) J Biol Chem 269, 5364-8.
13. Ghilardi, N. and Skoda, R.C. (1997) Mol Endocrinol 11, 393-9.
14. Lacronique, V. et al. (1997) Science 278, 1309-12.
15. Reiter, A. et al. (2005) Cancer Res 65, 2662-7.
16. Kralovics, R. et al. (2005) N Engl J Med 352, 1779-90.

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.