Phospho-PDGFR beta (Y740) Recombinant Rabbit Monoclonal Antibody [SN0646]

Function

Platelet Derived Growth Factor (PDGF) is a mitogen for mesenchyme- and glia-derived cells. PDGF consists of two chains, A and B, which dimerize to form functionally distinct isoforms, PDGF-AA, PDGF-AB, and PDGF-BB. These three isoforms bind with different affinities to two receptor types, a and b, which are endowed with protein tyrosine kinase domains and undergo either homo- or heterodimerization as a consequence of ligand binding. Ligand stimulation of PDGFR-b leads to autophosphorylation at Tyr-857, which is the major autophosphorylation site, and Tyr-751, which is the major in vitro phosphorylation site. Autophosphorylation of Tyr-751, which lies in the kinase insert region, is required for binding of phosphatidylinositol-3 kinase to the receptor. These auto-phosphorylation events largely contribute to signal transduction through the PDGF receptor. Mutations in PDGFRB are mainly associated with the clonal eosinophilia class of malignancies.

Background References

1. Kumar, A. et al. 2010. Platelet-derived growth factor-DD targeting arrests pathological angiogenesis by modulating glycogen synthase kinase-3beta phosphorylation. J. Biol. Chem. 285: 15500-15510.

2. Siegbahn, A. et al. 2008. TF/FVIIa transactivate PDGFRbeta to regulate PDGF-BB-induced chemotaxis in different cell types: involvement of Src and PLC. Arterioscler. Thromb. Vasc. Biol. 28: 135-141.

Sequence Similarity

Belongs to the protein kinase superfamily. Tyr protein kinase family. CSF-1/PDGF receptor subfamily.

Tissue Specificity

Weakly expressed in glomerular mesangial cells and interstitial cells. Up-regulated in areas of renal fibrosis. In mice with unilateral ureteral obstruction, increased expression in interstitial cells at day 4 and expression is markedly elevated at day 7 and is maximal at day 14.

Post-translational Modification

Autophosphorylated on tyrosine residues upon ligand binding. Autophosphorylation occurs in trans, i.e. one subunit of the dimeric receptor phosphorylates tyrosine residues on the other subunit. Phosphorylation at Tyr-578, and to a lesser degree, Tyr-580 is important for interaction with SRC. Phosphorylation at Tyr-715 is important for interaction with GRB2. Phosphorylation at Tyr-739 and Tyr-750 is important for interaction with PIK3R1. Phosphorylation at Tyr-750 is important for interaction with NCK1. Phosphorylation at Tyr-770 and Tyr-856 is important for interaction with RASA1/GAP. Phosphorylation at Tyr-856 is important for efficient phosphorylation of PLCG1 and PTPN11, resulting in increased phosphorylation of AKT1, MAPK1/ERK2 and/or MAPK3/ERK1, PDCD6IP/ALIX and STAM, and in increased cell proliferation. Phosphorylation at Tyr-1008 is important for interaction with PTPN11. Phosphorylation at Tyr-1008 and Tyr-1020 is important for interaction with PLCG1. Dephosphorylated by PTPRJ at Tyr-750, Tyr-856, Tyr-1008 and Tyr-1020 (By similarity). Dephosphorylated by PTPN2 at Tyr-578 and Tyr-1020.; N-glycosylated.; Ubiquitinated. After autophosphorylation, the receptor is polyubiquitinated, leading to its degradation.

Subcellular Location

Cell membrane, Cytoplasmic vesicle.

UNIPROT

SwissProt: P09619 Human

SwissProt: P05622 Mouse

SwissProt: Q05030 Rat

Synonyms