Phospho-SHP-1 (Tyr564) (D11G5) Rabbit mAb

• 产品编号：CST-8849S      品牌：CST       原厂货号：8849S
• 产品分类：抗体 > 一抗 > 磷酸化抗体
• 应用分类：

描述：

Phospho-SHP-1 (Tyr564) (D11G5) Rabbit mAb 兔单抗只能检测内源的在Tyr564位点磷酸化的 SHP-1蛋白。此单克隆抗体是通过合成人源对应的SHP-1 Tyr564位点周围的磷肽段来免疫动物而获得。SHP-1 (PTPN6) 是一个无受体蛋白酪氨酸磷酸化酶，主要在造血细胞中表达。此酶由两个SH2区域、一个酪氨酸磷酸化催化区域和一个C-末端调控区域构成(1)。SHP-1通过从目标蛋白去除磷酸基从而调控下游几个酪氨酸激酶调控的信号通路。在造血细胞中, SHP-1的N-末端SH2区域结合到酪氨酸磷酸化促红细胞生成素受体(EpoR) 从而负调控造血细胞的生长(2)。在表皮细胞中过表达SHP-1导致了Ros受体酪氨酸激酶的去磷酸化并发一系列的 Ros依赖的细胞增殖和转化的下调(3)。配体结合到骨髓细胞上后, SHP-1与IL-3R β 链相结合下调IL-3诱导的酪氨酸磷酸化和细胞增殖(4)。因为SHP-1下调各种增殖的通路, SHP-1被认为是潜在的肿瘤抑制因子和血管再生调节因子(5,6)。SHP-1 是Src家族激酶的底物(7,8) 在Tyr564位点的磷酸化被认为对其达到最大磷酸化能力有重要的作用(8)。在鼠科的慢性粒单核细胞白血病(CMML)模型中, 遗传抑制Tyr564 位点的磷酸化导致了转录因子Stat5组成型的过活化并加速CMML样疾病的发生(8)。

1. Yi, T.L. et al. (1992) Mol Cell Biol 12, 836-46.
2. Yi, T. et al. (1995) Blood 85, 87-95.
3. Keilhack, H. et al. (2001) J Cell Biol 152, 325-34.
4. Yi, T. et al. (1993) Mol Cell Biol 13, 7577-86.
5. Wu, C. et al. (2003) Gene 306, 1-12.
6. Bhattacharya, R. et al. (2008) J Mol Signal 3, 8.
7. Zhang, Z. et al. (2003) J Biol Chem 278, 4668-74.
8. Xiao, W. et al. (2010) Blood 116, 6003-13.

原厂资料：

Specificity / Sensitivity

Phospho-SHP-1 (Tyr564) (D11G5) Rabbit mAb recognizes endogenous levels of SHP-1 protein only when phosphorylated at Tyr564.

Source / Purification

Monoclonal antibody is produced by immunizing animals with a synthetic phosphopeptide corresponding to residues surrounding Tyr564 of human SHP-1 protein.

Background

SHP-1 (PTPN6) is a non-receptor protein tyrosine phosphatase that is expressed primarily in hematopoietic cells. The enzyme is composed of two SH2 domains, a tyrosine phosphatase catalytic domain, and a carboxy-terminal regulatory domain (1). SHP-1 removes phosphates from target proteins to downregulate several tyrosine kinase-regulated pathways. In hematopoietic cells, the amino-terminal SH2 domain of SHP-1 binds to tyrosine phosphorylated erythropoietin receptors (EpoR) to negatively regulate hematopoietic growth (2). Overexpression of SHP-1 in epithelial cells results in dephosphorylation of the Ros receptor tyrosine kinase and subsequent downregulation of Ros-dependent cell proliferation and transformation (3). Following ligand binding in myeloid cells, SHP-1 associates with the IL-3R β chain and downregulates IL-3-induced tyrosine phosphorylation and cell proliferation (4). Because SHP-1 downregulates various proliferation pathways, SHP-1 is considered a potential tumor suppressor and angiogenesis regulator (5,6).SHP-1 is a substrate of Src family kinases (7,8) and phosphorylation of Tyr564 is thought to be critical for achieving maximal phosphatase activity (8). In a murine model of chronic myelomonocytic leukemia (CMML), genetic suppression of Tyr564 phosphorylation led to constitutive overactivation of the transcription factor Stat5 and an accelerated onset of CMML-like disease (8).

1. Yi, T.L. et al. (1992) Mol Cell Biol 12, 836-46.
2. Yi, T. et al. (1995) Blood 85, 87-95.
3. Keilhack, H. et al. (2001) J Cell Biol 152, 325-34.
4. Yi, T. et al. (1993) Mol Cell Biol 13, 7577-86.
5. Wu, C. et al. (2003) Gene 306, 1-12.
6. Bhattacharya, R. et al. (2008) J Mol Signal 3, 8.
7. Zhang, Z. et al. (2003) J Biol Chem 278, 4668-74.
8. Xiao, W. et al. (2010) Blood 116, 6003-13.

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.