Phospho-PDGF Receptor β (Tyr1021) (6F10) Rabbit mAb

• 产品编号：CST-2227P      品牌：Cell Signaling Technology       原厂货号：2227P
• 产品分类：抗体 > 一抗 > 磷酸化抗体
• 应用分类：

描述：

磷酸化PDGF Receptor β (Tyr1021) (6F10) 兔单抗仅在Tyr1021被磷酸化后才能检测到PDGF receptor β的存在。本抗体也能与其它激活的PDGF受体家族的成员或其它激活的酪氨酸蛋白激酶发生交叉反应，如EGFR。单克隆抗体通过用多肽免疫动物得到，该磷酸化多肽是根据人的PDGF receptor β蛋白Tyr1021附近的氨基酸序列合成的。

血小板衍生生长因子(PDGF) 家族的蛋白以几种二硫键连接的二聚体形式存在 (PDGF AA, PDGF AB, PDGF BB, PDGF CC和PDGF DD)，它们以特定的方式与两种密切相关的酪氨酸激酶受体-PDGF receptor α (PDGFRα)和PDGF receptor β (PDGFRβ)-结合。PDGFRα 和PDGFRβ 的胞内激酶区有75% 到85% 的序列同源性，而激酶插入区和羧基端仅有很低的同源性(27% 到 28%) (1). PDGFRα 同型二聚体和除了含有PDGF D 之外的所有的PDGF亚型结合。PDGFRβ同型二聚体能结合PDGF BB 和DD亚型，还有PDGF AB 异二聚体。 异聚体 PDGF receptor α/β能结合 PDGF B, C, 和 D 同型二聚体，还有 PDGF AB 异二聚体 (2)。 PDGFRα 和 PDGFRβ 都能被PDGF激活和 EGFR形成异二聚体, (3)。各种细胞的受体总数、受体亚基组成都不相同，因此不同细胞对PDGF的反应也不同(4)。配体结合能诱发受体的二聚化和自磷酸化，继而结合并激活胞内含有SH2结构的信号传导分子， 如Grb2, Src, GAP, PI3K激酶, PLCγ和 Nck。激活的PDGFRs能引发一系列不同的信号通路 并影响细胞的生长、肌动蛋白重塑、迁移和分化 (5)。PDGFRβ激酶插入区的Tyr751位点结合PI3K激酶 (6)。根据PDGFRβ的Tyr751位点附近序列产生的磷酸化五肽(pTyr751-Val-Pro-Met-Leu)能够抑制PI3K激酶p85亚基的羧基端SH2区和PDGFRβ结合 (7)。 Tyr740对 PDGFRβ介导的 PI3 K激酶的激活也是必需的(8)。

PDGF激活PLCγ信号通路依赖于PDGF β 受体Tyr1009和 Tyr1021位点的自磷酸化 (8)。Tyr1009 或Tyr1021能分别或协同介导PDGF-BB 诱发的钙信号 (9)。

1. Deuel, T.F. et al. (1988) Biofactors 1, 213-217.
2. Bergsten, E. et al. (2001) Nat. Cell Biol. 3, 512-516.
3. Betsholtz, C. et al. (2001) Bioessays 23, 494-507.
4. Coughlin, S.R. et al. (1988) Prog. Clin. Biol. Res. 266, 39-45.
5. Ostman, A. and Heldin, C.H. (2001) Adv. Cancer Res. 80, 1-38.
6. Panayotou, G. et al. (1992) EMBO J. 11, 4261-4272.
7. Ramalingam, K. et al. (1995) Bioorg. Med. Chem. 3, 1263-1272.
8. Kashishian, A. et al. (1992) EMBO J. 11, 1373-1382.
9. Rönnstrand, L. et al. (1992) EMBO J 11, 3911-9.
10. Ridefelt, P. and Siegbahn, A. Anticancer Res 18, 1819-25.

原厂资料：

Specificity / Sensitivity

Phospho-PDGF Receptor β (Tyr1021) (6F10) Rabbit mAb detects endogenous levels of PDGF receptor β only when phosphorylated at tyrosine 1021. The antibody may cross-react with other activated PDGF receptor family members and other activated protein tyrosine kinases including EGFR.

Source / Purification

Monoclonal antibody is produced by immunizing animals with a synthetic phosphopeptide corresponding to residues surrounding Tyr1021 of human PDGF receptor β.

Background

The proteins of the platelet derived growth factor (PDGF) family exist as several disulphide-bonded, dimeric isoforms (PDGF AA, PDGF AB, PDGF BB, PDGF CC, and PDGF DD) that bind in a specific pattern to two closely related receptor tyrosine kinases, PDGF receptor α (PDGFRα) and PDGF receptor β (PDGFRβ). PDGFRα and PDGFRβ share 75% to 85% sequence homology between their two intracellular kinase domains while the kinase insert and carboxy-terminal tail regions display a lower level (27% to 28%) of homology (1). PDGFRα homodimers bind all PDGF isoforms except those containing PDGF D. PDGFRβ homodimers bind PDGF BB and DD isoforms, as well as the PDGF AB heterodimer. The heteromeric PDGF receptor α/β binds PDGF B, C, and D homodimers as well as the PDGF AB heterodimer (2). PDGFRα and PDGFRβ can each form heterodimers with EGFR, which is also activated by PDGF (3). Various cells differ in the total number of receptors present and in the receptor subunit composition, which may account for responsive differences among cell types to PDGF binding (4). Ligand binding induces receptor dimerization and autophosphorylation, followed by binding and activation of cytoplasmic SH2 domain-containing signal transduction molecules such as Grb2, Src, GAP, PI3 kinase, PLCγ, and Nck. A number of different signaling pathways are initiated by activated PDGF receptors and lead to control of cell growth, actin reorganization, migration, and differentiation (5). Tyr751 in the kinase-insert region of PDGFRβ is the docking site for PI3 kinase (6). Phosphorylated pentapeptides derived from Tyr751 of PDGFRβ (pTyr751-Val-Pro-Met-Leu) inhibit the association of the carboxy-terminal SH2 domain of the p85 subunit of PI3 kinase with PDGFRβ (7). Tyr740 is also required for PDGFRβ-mediated PI3 kinase activation (8).PDGF-stimulated PLCγ signaling is dependent on autophosphorylation of the PDGF β receptor at Tyr1009 and Tyr1021 (8). It was also shown that both Tyr1009 and Tyr1021 alone and in cooperation mediate PDGF-BB triggered calcium signalling (9).

1. Deuel, T.F. et al. (1988) Biofactors 1, 213-217.
2. Bergsten, E. et al. (2001) Nat. Cell Biol. 3, 512-516.
3. Betsholtz, C. et al. (2001) Bioessays 23, 494-507.
4. Coughlin, S.R. et al. (1988) Prog. Clin. Biol. Res. 266, 39-45.
5. Ostman, A. and Heldin, C.H. (2001) Adv. Cancer Res. 80, 1-38.
6. Panayotou, G. et al. (1992) EMBO J. 11, 4261-4272.
7. Ramalingam, K. et al. (1995) Bioorg. Med. Chem. 3, 1263-1272.
8. Kashishian, A. et al. (1992) EMBO J. 11, 1373-1382.
9. Rönnstrand, L. et al. (1992) EMBO J 11, 3911-9.
10. Ridefelt, P. and Siegbahn, A. Anticancer Res 18, 1819-25.

注意事项：

For Research Use Only. Not For Use In Diagnostic Procedures.

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.