Phospho-Gab2 (Tyr452) (C33G1) Rabbit mAb

• 产品编号：CST-3882S      品牌：CST       原厂货号：3882S
• 产品分类：抗体 > 一抗 > 磷酸化抗体
• 应用分类：

描述：

Phospho-Gab2 (Tyr452) (C33G1) Rabbit mAb能够检测Tyr452位点磷酸化的内源性Gab2蛋白含量。该抗体可以和酪氨酸磷酸化的Gab1和Gab3发生微弱的交叉反应。该单克隆抗体是采用合成的与人源Gab2蛋白Tyr452位点周围序列相对应的磷酸化肽段免疫动物而生产的。Grb相关结合因子（Gab）家族是一类由多种受体酪氨酸激酶（RTKs），如EGFR，HGFR，胰岛素受体，细胞因子受体和B细胞抗原受体招募的接头蛋白。RTKs受到它们的同源配体刺激后，Gab被招募到细胞膜上，接着其被磷酸化，并起到支架的作用（1-4）。Gab1蛋白存在多个酪氨酸磷酸化位点（5）。酪氨酸（472位点）磷酸化可以调节其与PI3激酶p85的结合（6,7）。Gab1酪氨酸（307，373和407位点）的磷酸化可以调节Gab1与PLCγ的互作（8）。酪氨酸（627和659位点）磷酸化是Gab1结合并活化蛋白酪氨酸磷酸酶SHP2所必需的（6,9）。Gab2可以被酪氨酸激酶磷酸化（10,11），Tyr452是P85（PI3K激酶的调节亚基）的潜在结合位点。Tyr614对SHP2结合必不可少（11），另外，Akt在Ser159位磷酸化Gab2并抑制其酪氨酸磷酸化，这表明Akt参与了Gab2信号通路的负调控（12）。

1. Holgado-Madruga, M. et al. (1996) Nature 379, 560-564.
2. Weidner, K.M. et al. (1996) Nature 384, 173-176.
3. Takahashi-Tezuka, M. et al. (1998) Mol. Cell. Biol. 18, 4109-4117.
4. Ingham, R.J. et al. (2001) J Biol Chem 276, 12257-65.
5. Lehr, S. et al. (1999) Biochemistry 38, 151-159.
6. Rocchi, S. et al. (1998) Mol. Endocrinol. 12, 914-923.
7. Yu, C.F. et al. (2001) J Biol Chem 276, 32552-8.
8. Gual, P. et al. (2000) Oncogene 19, 1509-18.
9. Cunnick, J.M. et al. (2001) J Biol Chem 276, 24380-7.
10. Gadina, M. et al. (2000) J. Biol. Chem. 275, 26959-26966.
11. Yamasaki, S. et al. (2001) J. Biol. Chem. 276, 45175-451783.
12. Crouin, C. et al. (2001) FEBS Lett. 495, 148-153.
13. Lynch, D.K. and Daly, R.J. (2002) EMBO J. 21, 72-82.

原厂资料：

Specificity / Sensitivity

Phospho-Gab2 (Tyr452) (C33G1) Rabbit mAb detects endogenous levels of Gab2 only when phosphorylated at Tyr452. This antibody weakly cross-reacts with tyrosine-phosphorylated Gab1 and Gab3 proteins.

Source / Purification

Monoclonal antibody is produced by immunizing animals with a synthetic phosphopeptide corresponding to residues surrounding Tyr452 of human Gab2.

Background

The Grb-associated binder (Gab) family is a family of adaptor proteins recruited by a wide variety of receptor tyrosine kinases (RTKs) such as EGFR, HGFR, insulin receptor, cytokine receptor and B cell antigen receptors. Upon stimulation of RTKs by their cognate ligand, Gab is recruited to the plasma membrane where it is phosphorylated and functions as a scaffold (1-4). Multiple tyrosine phosphorylation sites of Gab1 protein have been identified (5). Phosphorylation of Tyr472 regulates its binding to p85 PI3 kinase (6,7). Phosphorylation of Gab1 at Tyr307, Tyr373 and Tyr407 modulates its association to PLCγ (8). Phosphorylation of Tyr627 and Tyr659 is required for Gab1 binding to and activation of the protein tyrosine phosphatase SHP2 (6,9).Gab2 is also phosphorylated by tyrosine kinases (10,11). Tyr452 is a potential binding site of p85, the regulatory subunit of PI3 kinase (12). Tyr614 is essential for SHP2 association (11). Furthermore, Akt phosphorylates Gab2 at Ser159 and inhibits Gab2 tyrosine phosphorylation, suggesting that Akt is engaged in negative feedback regulation of Gab2 signaling (13).

1. Holgado-Madruga, M. et al. (1996) Nature 379, 560-564.
2. Weidner, K.M. et al. (1996) Nature 384, 173-176.
3. Takahashi-Tezuka, M. et al. (1998) Mol. Cell. Biol. 18, 4109-4117.
4. Ingham, R.J. et al. (2001) J Biol Chem 276, 12257-65.
5. Lehr, S. et al. (1999) Biochemistry 38, 151-159.
6. Rocchi, S. et al. (1998) Mol. Endocrinol. 12, 914-923.
7. Yu, C.F. et al. (2001) J Biol Chem 276, 32552-8.
8. Gual, P. et al. (2000) Oncogene 19, 1509-18.
9. Cunnick, J.M. et al. (2001) J Biol Chem 276, 24380-7.
10. Gadina, M. et al. (2000) J. Biol. Chem. 275, 26959-26966.
11. Yamasaki, S. et al. (2001) J. Biol. Chem. 276, 45175-451783.
12. Crouin, C. et al. (2001) FEBS Lett. 495, 148-153.
13. Lynch, D.K. and Daly, R.J. (2002) EMBO J. 21, 72-82.

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.