Platelet-derived growth factor receptor alpha (PDGFRα) homodimer (PDGFRαα)

The Platelet-derived growth factor receptor alpha (PDGFRα) homodimer is a cell-surface tyrosine kinase receptor formed by the dimerization of two alpha subunits upon binding with PDGF ligands, primarily PDGF-AA, -AB, -BB, and -CC (UniProt: P16234). This dimerization triggers autophosphorylation of intracellular tyrosine residues, initiating signaling cascades such as the PI3K/AKT and Ras/MAPK pathways that regulate cell growth, chemotaxis, and survival, particularly in mesenchymal cells (NCBI Gene ID: 5156). In clinical contexts, PDGFRα is a significant therapeutic target due to its involvement in various cancers where it is often overexpressed or constitutively activated by mutations (PMID: 15139068). For instance, specific mutations like D842V in the PDGFRA gene are key drivers in a subset of gastrointestinal stromal tumors (GIST) and are often resistant to standard treatments. Additionally, the FIP1L1-PDGFRA fusion protein is a hallmark of certain hypereosinophilic syndromes, leading to constitutive kinase activity (PMID: 12660387). Pharmacological intervention typically involves small-molecule tyrosine kinase inhibitors like imatinib or avapritinib, which target the ATP-binding site, or monoclonal antibodies like olaratumab that prevent receptor activation by blocking ligand interaction (DrugBank: DB00619, DB14746).

Other names

PDGFR-alpha homodimerPDGFR-AACD140A homodimerPlatelet-derived growth factor receptor 1 homodimerPDGFRA/PDGFRA dimer

Small molecule inhibitors typically act as ATP-competitive inhibitors of the intracellular kinase domain, while monoclonal antibodies bind the extracellular domain to prevent ligand-induced dimerization and activation (PMID: 28257204).