Stem cell factor receptor (c-Kit) and Platelet-derived growth factor receptor alpha (PDGFRα) (c-Kit; PDGFRα)

c-Kit (stem cell receptor, CD117) and PDGFRα (platelet-derived growth factor receptor alpha, CD140a) are closely related transmembrane receptor tyrosine kinases within the type III subclass and structurally characterized by five extracellular immunoglobulin-like domains, a single transmembrane region, and an intracellular split kinase domain[1][3][2][6]. Both receptors regulate key cellular processes such as proliferation, differentiation, and survival by activating downstream signal transduction pathways upon ligand-mediated dimerization and autophosphorylation. Mutations or aberrant activation of c-Kit or PDGFRα play an oncogenic role in multiple tumor types, most notably in gastrointestinal stromal tumors (GISTs), where these mutations are frequently used as diagnostic and predictive biomarkers[7][5]. Inhibitors targeting their kinase activity (e.g., imatinib, avapritinib, ripretinib) are established therapies, but resistance due to secondary mutations remains a major clinical challenge. c-Kit also plays essential roles in normal hematopoiesis, melanogenesis, gametogenesis, and mast cell function, while PDGFRα is fundamental for stromal and mesenchymal cell development, and the maintenance of certain interstitial cell networks[1][3][6].

Other names

CD117KITStem cell factor receptorSCFRPDGF receptor alphaCD140a

Inhibition of kinase activity, preventing downstream signal transduction (competitive ATP binding site inhibitors); Prevention of receptor autophosphorylation and dimerization, blocking activation; Inhibition leads to reduced cell proliferation and increased apoptosis in tumors dependent on these pathways