Phospho-c-Cbl (Tyr700) (D16D7) Rabbit mAb

• 产品编号：CST-8869P      品牌：Cell Signaling Technology       原厂货号：8869P
• 产品分类：抗体 > 一抗 > 磷酸化抗体
• 应用分类：

描述：

Phospho-c-Cbl (Tyr700) (D16D7) Rabbit mAb兔单抗只识别内源性的Tyr700磷酸化c-Cbl蛋白。该单克隆抗体经合成与人c-Cbl蛋白Tyr700的邻近氨基酸残基序列一致，免疫动物产生。c-Cbl原癌基因是一种广泛表达的细胞质衔接蛋白，主要表达于造血细胞(1,2)。对于许多种细胞表面受体的刺激，c-Cbl迅速地进行酪氨酸磷酸化，并与许多细胞内信号分子例如蛋白酪氨酸激酶，磷脂酰肌醇-3激酶，Crk和14-3-3蛋白相联合(3,4)。c-Cbl具有高度保守的氨基末端磷酸酪氨酸结合结构域(TKB)，以及C3HC4 RING指模序。TKB识别活化的酪氨酸激酶受体(RTKs)上的磷酸化的酪氨酸，以及其他非受体酪氨酸激酶。环指模序募集泛素缀合酶。这两种结构域主要负责c-Cbl的泛素连接酶活性，以及RTKs的下调(3)。研究表明人癌症组织，c-Cbl以一种肿瘤特异的方式频繁地进行酪氨酸磷酸化(5)。c-Cbl Tyr731的磷酸化为下游的信号组分诸如p85 和 Fyn提供了一个停泊位点(6)。c-Cbl在Tyr700磷酸化，主要由Fyn, Yes和Syk (4)以及Vav，一种局限于造血细胞中的Rac鸟嘌呤核苷酸交换因子，募集到磷酸化的Tyr700并进行c-Cbl-依赖的泛素化作用(5)。

1. Blake, T.J. et al. (1991) Oncogene 6, 653-657.
2. Thien, C.B. and Langdon, W.Y. (1998) Immunol. Cell Biol. 76, 473-482.
3. Christine, B.F. et al. (2001) Nat. Rev. Mol. Cell Biol. 2, 294-307.
4. Feshchenko, E.A. et al. (1998) J. Biol. Chem. 273, 8323-8331.
5. Kamei, T. et al. (2000) Int. J. Oncol. 17, 335-339.
6. Hunter, C. et al. (1999) J. Biol. Chem. 274, 2097-2106.
7. Miura-Shimura, Y. et al. (2003) J Biol Chem 278, 38495-504.

原厂资料：

Homology

Species predicted to react based on 100% sequence homology: Mouse

Specificity / Sensitivity

Phospho-c-Cbl (Tyr700) (D16D7) Rabbit mAb recognizes endogenous levels of c-Cbl protein only when phosphorylated at Tyr700.

Source / Purification

Monoclonal antibody is produced by immunizing animals with a synthetic phosphopeptide corresponding to residues surrounding Tyr700 of human c-Cbl protein.

Background

The c-Cbl proto-oncogene is a ubiquitously expressed cytoplasmic adaptor protein that is especially predominant in hematopoietic cells (1,2). c-Cbl is rapidly tyrosine-phosphorylated in response to stimulation of a variety of cell-surface receptors and becomes associated with a number of intracellular signaling molecules such as protein tyrosine kinases, phosphatidylinositol-3 kinase, Crk, and 14-3-3 proteins (3,4). c-Cbl possesses a highly conserved amino-terminal phosphotyrosine binding domain (TKB) and a C3HC4 RING finger motif. The TKB recognizes phosphorylated tyrosines on activated receptor tyrosine kinases (RTKs) as well as other nonreceptor tyrosine kinases. The RING finger motif recruits ubiquitin-conjugating enzymes. These two domains are primarily responsible for the ubiquitin ligase activity of c-Cbl and downregulation of RTKs (3). Research studies have indicated that in human cancer tissues, c-Cbl is frequently tyrosine-phosphorylated in a tumor-specific manner (5). Phosphorylation of Tyr731 of c-Cbl provides a docking site for downstream signaling components such as p85 and Fyn (6).It has been demonstrated that c-Cbl is phosphorylated at Tyr700 by Fyn, Yes, and Syk (4) and that Vav, a hematopoietic-restricted Rac guanine nucleotide exchange factor, undergoes c-Cbl-dependent ubiquitination upon recruitment to phospho-Tyr700 (5).

1. Blake, T.J. et al. (1991) Oncogene 6, 653-657.
2. Thien, C.B. and Langdon, W.Y. (1998) Immunol. Cell Biol. 76, 473-482.
3. Christine, B.F. et al. (2001) Nat. Rev. Mol. Cell Biol. 2, 294-307.
4. Feshchenko, E.A. et al. (1998) J. Biol. Chem. 273, 8323-8331.
5. Kamei, T. et al. (2000) Int. J. Oncol. 17, 335-339.
6. Hunter, C. et al. (1999) J. Biol. Chem. 274, 2097-2106.
7. Miura-Shimura, Y. et al. (2003) J Biol Chem 278, 38495-504.

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