The gene encoding the α-subunit of the PDGFRA maps to band q12 of chromosome 4. The gene contains 23 exons spanning about 65 kb. The first noncoding exon is followed by a large intron of approximately 23 kb (Gronwald et al., 1990; Kawagishi et al., 1995). An important paralog of PDGFRA is FLT4.

6.4-kb transcript; coexpressed with the 5.3-kb PDGF receptor mRNA.

Size: 1089 amino acids; molecular weight: 122670 Da.
Subunit: Interacts with dimeric PDGFA, PDGFB and/or PDGFC; heterodimers with PDGFRB. Present in an inactive conformation as a monomer in the absence of bound ligand.

PDGFR expression is characteristic of various mesodermal derivatives; specially expressed in the urinary tracts and in male and female genitals.

Subcellular location: cell membrane.

Member of the type III class of tyrosine kinase receptors which also includes c-KIT, FLT3 and the macrophage-colony-stimulating factor receptor; characterized by five immunoglobuline-like extracellular domains; a single-spanning transmembrane domain and an intracellular split kinase domain, connected by a flexible polypeptide insert; structurally homologous to c-KIT. PDGFA has transmembrane receptor protein tyrosine kinase activity and acts as a cell-surface receptor for members of the platelet-derived growth factor family: PDGFA, PDGFB and PDGFC, which are mitogens for fibroblasts and cells of mesenchymal origin origin. It plays an essential role in the regulation of many biological processes including cell proliferation, survival, differentiation and cell migration. Plays an important role in embryonic development, in the adult control tissue homeostasis in various organs including kidney, epidydimis, lung and pancreas; required for normal development of intestinal villi in the gastrointestinal tract, plays a role in platelet activation, wound healing and angiogenesis (Demoulin et al., 2012; Heldin et al., 2013).
Regulation: Function as homo- and/or heterodimers depending on the cell type; activated by ligand-induced dimerization and autophosphorylation on specific tyrosine residues upon binding. Activation of the intracellular kinase activity of the receptor leads to creation of docking sites for signal transduction molecules. Subsequent phosphorylation of its substrates initiates a variety of signal transduction cascades that promotes cell proliferation, survival and migration through the PI3K-AKT-mTOR and RAS-MAPK pathways as well as promotes activation of STAT family members (JAK/STAT) (Demoulin et al., 2012).

Mutations in the PDGFRA gene contribute to the pathophysiology of various diseases such as atherosclerosis, abnormalities of the tubal neural development and fibrotic diseases. In cancer, activating point mutations, gene amplifications and chromosomal rearrangements including gene fusions and chromosomal deletions have been found in certain malignancies. These include hematological malignancies such as acute myeloid leukemia, atypical chronic myelogenous leukemia, chronic myelomonocytic leukemia, eosinophilic disorders and mastocytosis (Gotlib et al., 2008). PDGFRA mutations also have been described in somatic and familial gastrointestinal stromal tumors, synovial sarcomas, glioblastoma, malignant peripheral nerve sheath tumors, melanoma and a in a variety of other cancers (Chompret et al., 2004; Heinrich et al., 2003).