KIT proto-oncogene receptor tyrosine kinase (KIT) (KIT)

KIT proto-oncogene receptor tyrosine kinase, commonly known as c-Kit or CD117, is a type III receptor tyrosine kinase essential for the development and survival of several cell types, including hematopoietic stem cells, mast cells, and melanocytes [4, 7]. Upon binding its ligand, stem cell factor (SCF), the receptor undergoes dimerization and autophosphorylation of its intracellular kinase domain, which initiates signaling cascades such as the PI3K/AKT and RAS/MAPK pathways [2, 11]. These pathways regulate critical cellular processes like proliferation, differentiation, and migration [1, 8]. Dysregulation of KIT, often through gain-of-function mutations, is a hallmark of various diseases, particularly gastrointestinal stromal tumors (GIST), systemic mastocytosis, and certain types of leukemia [3, 6]. Because of its central role in these pathologies, KIT is a primary target for tyrosine kinase inhibitors (TKIs) like imatinib and sunitinib [10, 12]. However, therapeutic challenges include the development of resistance mutations, which has led to the clinical use of more selective or broad-spectrum inhibitors like ripretinib and avapritinib [6, 8].

Other names

c-KitCD117Mast/stem cell growth factor receptorSCFRTyrosine-protein kinase KITPiebald trait proteinPBTv-kit

Tyrosine kinase inhibition through competitive binding to the ATP-binding site, preventing autophosphorylation and downstream signaling.