KIT and PDGFRA Receptor Tyrosine Kinases (KIT/PDGFRA)

KIT (KIT proto-oncogene, receptor tyrosine kinase) and PDGFRA (platelet-derived growth factor receptor alpha) are closely related type III receptor tyrosine kinases found on the cell surface. Upon binding their respective ligands (stem cell factor for KIT, platelet-derived growth factor isoforms for PDGFRA), these receptors dimerize and activate their intrinsic kinase domains, leading to autophosphorylation and initiation of downstream signaling cascades critical for cell proliferation, migration, differentiation, and survival. Mutations in these receptors lead to constitutive activation, driving the pathogenesis of gastrointestinal stromal tumors and other malignancies. Therapeutic inhibition of these mutant kinases forms the basis of targeted therapy in oncology, with their mutational status serving as essential biomarkers for drug selection and resistance.

Other names

c-KITCD117Stem cell factor receptorSCFRCD140aPDGFR-alphaPlatelet-derived growth factor receptor alpha

Competitive inhibition of the ATP-binding site of the tyrosine kinase domain; Blockade of downstream signaling required for proliferation and survival