Product Pathways - Tyrosine Kinase/ Adaptors
Phospho-PDGF Receptor β (Tyr1021) (6F10) Rabbit mAb #2227
| Applications | Reactivity | Sensitivity | MW (kDa) | Isotype |
|---|---|---|---|---|
| W | H M | Endogenous | 190 | Rabbit IgG |
Applications Key:
W=Western Blotting
Reactivity Key:
H=Human
M=Mouse
Species cross-reactivity is determined by Western blot.
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 antibodies are produced by immunizing rabbits with a synthetic phospho-peptide (KLH-coupled) 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). PDGF Receptor α homodimers bind all PDGF isoforms except those containing PDGF D. PDGF Receptor β homodimers bind PDGF BB and DD isoforms, as well as the PDGF AB heterodimer. The heteromeric PDGF α/β receptor 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).
- Deuel, T.F. et al. (1988) Biofactors 1, 213-217.
- Bergsten, E. et al. (2001) Nat. Cell Biol. 3, 512-516.
- Betsholtz, C. et al. (2001) Bioessays 23, 494-507.
- Coughlin, S.R. et al. (1988) Prog. Clin. Biol. Res. 266, 39-45.
- Ostman, A. and Heldin, C.H. (2001) Adv. Cancer Res. 80, 1-38.
- Panayotou, G. et al. (1992) EMBO J. 11, 4261-4272.
- Ramalingam, K. et al. (1995) Bioorg. Med. Chem. 3, 1263-1272.
- Kashishian, A. et al. (1992) EMBO J. 11, 1373-1382.
- Ronnstrand, L. et al. (1992) EMBO J. 11, 3911-9.
- Ridefelt, P. and Siegbahn, A. Anticancer Res. 18, 1819-25.
Application References
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Rabbit Monoclonals Produced Using Epitomics® Technology, U.S. Patent No. 5,675,063.
This product is for in vitro research use only and is not intended for use in humans or animals. This product is not intended for use as therapeutic or in diagnostic procedures.