Platelet-derived growth factor receptor alpha and beta (PDGFRα and PDGFRβ) (PDGFRα/β)

Platelet-derived growth factor receptors alpha and beta (PDGFRα and PDGFRβ) are cell-surface receptor tyrosine kinases (RTKs) that play a fundamental role in regulating cell proliferation, migration, and survival [2, 4]. These receptors are activated upon binding of their cognate ligands (PDGF-A, -B, -C, and -D), which induces receptor dimerization and subsequent autophosphorylation of the intracellular kinase domains [3, 7]. This phosphorylation event creates docking sites for signaling molecules, triggering downstream cascades such as the PI3K/AKT, RAS/MAPK, and PLC-γ pathways [3, 6]. In healthy tissues, PDGFR signaling is essential for embryonic development, wound healing, and the maintenance of connective tissue [9, 11]. However, aberrant activation of these receptors—often through genetic mutations, gene fusions, or overexpression—is strongly linked to the pathogenesis of various malignancies, including gastrointestinal stromal tumors (GIST), glioblastomas, and certain leukemias [1, 11, 12]. Additionally, dysregulated PDGFR signaling contributes to fibrotic diseases and cardiovascular disorders like atherosclerosis [2, 3]. Therapeutic strategies targeting the PDGFR kinase domains primarily utilize small molecule tyrosine kinase inhibitors (TKIs) such as imatinib and sunitinib, which compete with ATP for binding to the catalytic site, thereby blocking downstream signaling and inhibiting tumor growth [4, 10, 13].

Other names

PDGFRAPDGFRBCD140aCD140bPlatelet-derived growth factor receptor 1Platelet-derived growth factor receptor 2PDGFR-alphaPDGFR-betaPDGFR kinase

Tyrosine kinase inhibition via ATP-competitive binding to the intracellular kinase domains, preventing autophosphorylation and downstream signaling.