Digestive disorders

III./2.4.: The c-kit/CD117 

KIT is a proto-oncogen. Its product is a 145-160 kDa sized, type III. transmembrane tyrosine kinase receptor protein, also called as mastocyte/stem cell growth factor receptor (SCFR) , or c-kit/CD117-protein. Structurally and functionally it is closely related to the PDGF (platelet derived growth factor) and M-CSF (macrophage colony stimulating factor) proteins. First described by German biochemist Axel Ullrich (1987), gene location was found on the long arm of chromosome 4 (4q11-12). The c-kit/CD117-receptor itself consist of a ligand-binding extracellular domain, a transmembrane domain, a juxtamembrane domain and two cytoplasmatic tyrosine kinase domain (TK-I. and TK-II.).

When binding its ligand, the stem cell factor (SCF, an early haemopoetic growth factor), two c-kit/CD117 molecule binds together, which is called the receptor’s dimerization. This leads to a chain of further cytoplasmatic molecular reactions. In this course, specific tyrosine locations are phosphorylated, binding signal transduction molecules which also go through phosphorylation and often are kynases as well. Signal transduction pathways set afloat influence cell proliferation, adhesion, apoptosis and differentiation. Out of the signalling pathways common in these receptor types, c-kit/CD117-receptor uses RAS-RAF-MAPK, PI3K-AKT-mTOR and JAK-STAT pathways. PDGFRA  is characterized by pathways that are partly different from those of the c-kit/CD117.