Platelet-derived growth factor receptor and KIT proto-oncogene, receptor tyrosine kinase (PDGFR and KIT)

PDGFR (platelet-derived growth factor receptor) and KIT (KIT proto-oncogene, receptor tyrosine kinase) are cell-surface transmembrane proteins belonging to the type III receptor tyrosine kinase family[2][3][6]. They share similar structural features: five extracellular immunoglobulin-like domains, a single transmembrane helix, and a split intracellular kinase domain[2][4]. Activation occurs through ligand-mediated dimerization, autophosphorylation, and initiation of downstream signaling cascades, notably PI3K/AKT, RAS/RAF/MAPK, and JAK/STAT pathways[1][3]. PDGFR and KIT regulate embryonic development, tissue homeostasis, wound healing, and hematopoiesis[5][8]. Mutations or aberrant activation contribute to several diseases, especially cancers such as GIST and certain leukemias, making them prime drug targets. Multiple kinase inhibitors have been developed and approved for diseases driven by these receptors[6]. Their clinical utility is influenced by mutational status and tissue expression, with resistance mutations posing ongoing therapeutic challenges[1][6].

Other names

Platelet-derived growth factor receptor (alpha and beta forms: PDGFRα, PDGFRβ)CD140a (PDGFRα)CD140b (PDGFRβ)Stem cell factor receptorCD117c-KITKIT receptor

Small molecule inhibitors (e.g., imatinib, sunitinib) block the kinase activity by occupying the ATP-binding pocket, preventing phosphorylation and downstream signaling. Some antibodies or ligands induce receptor internalization or inhibit ligand binding.