PDGFRA

PDGFRA, or platelet-derived growth factor receptor alpha, is a receptor tyrosine kinase encoded by the PDGFRA gene in humans. It is part of the PDGFR family and is expressed in various mesenchymal and vascular cell types. PDGFR-α is activated by binding of platelet-derived growth factor ligands and participates in signaling pathways that regulate cell proliferation, survival, migration, and angiogenesis. Aberrations in PDGFRA, including mutations or gene fusions, are linked to several human diseases, particularly certain cancers and myeloid disorders.

PDGFRA encodes a transmembrane protein with an extracellular ligand-binding domain containing five immunoglobulin-like loops, a single transmembrane helix, and an intracellular tyrosine kinase domain. Ligand binding induces receptor dimerization and autophosphorylation of tyrosine residues, creating docking sites for signaling proteins and triggering downstream pathways such as PI3K-AKT, RAS-MAPK, and PLCγ, which control cell cycle progression, survival, and migration.

PDGF receptor alpha binds several PDGF family ligands, most notably PDGF-AA and PDGF-BB, and can be activated by others such as PDGF-AB and PDGF-CC in certain contexts. Activation leads to signaling that coordinates development, tissue repair, and vascular biology, including roles in smooth muscle cell behavior and pericyte recruitment.

In oncology, activating PDGFRA mutations or gene fusions drive disease in subsets of gastrointestinal stromal tumors (GISTs) and chronic eosinophilic leukemia with FIP1L1-PDGFRA fusion. PDGFRA amplification or overexpression is observed in gliomas and other cancers. Therapeutically, PDGFR inhibitors such as imatinib, sunitinib, and ponatinib are used in PDGFRA-driven disease; some mutations, such as D842V in exon 18, confer resistance to imatinib, prompting use of alternative agents like avapritinib for GIST. Diagnostic testing includes sequencing for mutations and FISH for fusions.