PDGF Receptor beta antibody

Platelet derived growth factor (PDGF), the major mitogen in serum for cultured connective tissue cells, exerts it actions via specific receptors on the cell surface. Two distinct human PDGF receptor transmembrane binding proteins have been identified, a 170 kDa, 1066 amino acid residue alpha-receptor (PDGF Ralpha) and a 190 kDa, 1074 amino acid residue beta-receptor (PDGF Rbeta). The two receptor proteins are structurally related and consist of an extracellular portion containing five immunoglobulin-like domains, a single transmembrane region, and an intracellular portion with a protein-tyrosine kinase domain. Ligand binding induces receptor dimerization and autophosphorylation, allowing binding and activation of cytoplasmic SH2-domain containing signal transduction molecules. Thereby, a number of different signaling pathways are initiated leading to cell growth, actin reorganization, migration and differentiation. Recent observations suggest that extensive cross-talk occurs between different signaling pathways, and that stimulatory signals are modulated by inhibitory signals arising in parallel. Between the two PDGF receptors, there is 44% overall sequence identity. Within the extracellular domain, 30% of the amino acid residues are identical. The different isoforms of PDGF (PDGF-AA, PDGF-AB and PDGF-BB) bind with different affinities to two distinct receptors. Ligand-binding induces receptor dimerization; the A-subunit of PDGF binds to alpha-receptors, whereas the B-subunit binds to both alpha- and beta-receptors. Binding of PDGF to its receptor activates the tyrosine kinase domain and leads to enhanced phosphorylation of intracellular substrates as well as to autophosphorylation of the receptor itself. In addition, several other cellular responses are induced. Studies have indicated that PDGF beta-receptors are not present on most cells of normal tissues, but are upregulated, in conjunction with inflammation, excess cell proliferation, malignancytic, and fibrotic conditions.