Platelet-derived growth factor receptor alpha homodimer (PDGFRA homodimer)

The Platelet-derived growth factor receptor alpha (PDGFRA) homodimer is a cell surface receptor tyrosine kinase that plays a critical role in regulating cell proliferation, survival, and migration, particularly in mesenchymal cells (UniProt P16234; NCBI Gene 5156). Upon binding of its ligands, such as PDGF-AA, PDGF-BB, or PDGF-CC, the receptor subunits undergo dimerization and autophosphorylation, initiating downstream signaling pathways like PI3K/AKT, MAPK, and STAT (PMID: 29158374). In healthy physiology, it is essential for embryonic development, wound healing, and the maintenance of connective tissue (NCBI Gene 5156). However, dysregulation of the PDGFRA homodimer through gene mutations, amplifications, or fusions is a major driver in several malignancies, including gastrointestinal stromal tumors (GIST) and certain types of leukemia (PMID: 15184875). Therapeutic strategies often involve small-molecule tyrosine kinase inhibitors like imatinib or avapritinib that block the intracellular kinase activity, or monoclonal antibodies like olaratumab that target the extracellular domain (FDA Label: Ayvakit; ClinicalTrials.gov). Monitoring for specific mutations, such as the D842V substitution, is crucial for determining drug sensitivity and guiding clinical management in oncology (PMID: 15184875).

Other names

PDGFR-alpha homodimerCD140A homodimerAlpha-type platelet-derived growth factor receptor homodimerPDGFRα homodimerPDGFRA/PDGFRA complex

Inhibition of the intracellular tyrosine kinase domain to prevent autophosphorylation or blocking the extracellular ligand-binding domain to prevent receptor dimerization and subsequent downstream signaling cascades.