Proto-oncogene tyrosine-protein kinase Kit (KIT)

Proto-oncogene tyrosine-protein kinase Kit (KIT, also known as CD117) is a type III transmembrane receptor tyrosine kinase expressed on various stem/progenitor cells including hematopoietic stem cells, germ cells, melanocytes, mast cells, and interstitial cells of Cajal. Its ligand is stem cell factor (SCF, also called steel factor). Upon SCF binding, KIT dimerizes and activates its intrinsic protein tyrosine kinase activity through autophosphorylation. This triggers multiple downstream pathways controlling cellular processes such as proliferation, survival, differentiation, migration—critical for blood formation (hematopoiesis), pigment production (melanogenesis), gamete development (gametogenesis), gastrointestinal motility via ICCs—and immune responses via mast cells. Gain-of-function mutations lead to constitutive activation implicated in several cancers—notably gastrointestinal stromal tumors (GISTs), acute myeloid leukemia (AML), melanoma—and rare disorders like systemic mastocytosis. Loss-of-function causes developmental syndromes such as piebaldism due to defective melanocyte migration. Therapeutically relevant because small-molecule inhibitors can block mutant/overactive forms; however resistance often emerges through additional genetic changes within the gene encoding this protein. Normal tissue toxicity remains an important consideration given its role across multiple organ systems.

Other names

c-KitCD117mast/stem cell growth factor receptor (SCFR)p145 c-kitPBTpiebald trait proteinproto-oncogene c-Kitv-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog

Drugs targeting KIT typically act as tyrosine kinase inhibitors, binding to the ATP-binding site of the intracellular domain of the receptor. This blocks autophosphorylation/activation of downstream signaling pathways that drive proliferation/survival in cancer cells with activating mutations. Some drugs preferentially bind inactive conformations.