PDGFRB

Platelet-derived growth factor receptor beta is a protein that in humans is encoded by the PDGFRB gene. Mutations in PDGFRB are mainly associated with the clonal eosinophilia class of malignancies.

Gene

The PDGFRB gene is located on human chromosome 5 at position q32 (designated as 5q32) and contains 25 exons. The gene is flanked by the genes for granulocyte-macrophage colony-stimulating factor and Colony stimulating factor 1 receptor (also termed macrophage-colony stimulating factor receptor), all three of which may be lost together by a single deletional mutation thereby causing development of the 5q-syndrome. Other genetic abnormalities in PDGFRB lead to various forms of potentially malignant bone marrow disorders: small deletions in and chromosome translocations causing fusions between PDGFRB and any one of at least 30 genes can cause Myeloproliferative neoplasms that commonly involve eosinophilia, eosinophil-induced organ injury, and possible progression to aggressive leukemia (see below).

Structure

The PDGFRB gene encodes a typical receptor tyrosine kinase, which belongs to the type III tyrosine kinase receptor (RTK) family and is structurally characterized by five extracellular immunoglobulin-like domains, a single membrane-spanning helix domain, an intracellular juxtamembrane domain, a split tyrosine kinase domain and a carboxylic tail. In the absence of ligand, PDGFRβ adopts an inactive conformation in which the activation loop folds over the catalytic site, the juxtamembrane region over a loop occluding the active site and the carboxy-terminal tail over the kinase domain. Upon PDGF binding the dimerization of receptor releases the inhibitory conformations due to auto-phosphorylation of regulatory tyrosine residues in trans fashion. Tyrosine residues 857 and 751 are major phosphorylation sites for the activation of PDGFRβ.

The molecular mass of the mature, glycosylated PDGFRβ protein is approximately 180 kDa.