Structural basis for stem cell factor–KIT signaling and activation of class III receptor tyrosine kinases

摘要: Stem cell factor (SCF) binds to and activates the KIT receptor, a class III receptor tyrosine kinase (RTK), stimulate diverse processes including melanogenesis, gametogenesis hematopoeisis. Dysregulation of activation is associated with many cancers. We report 2.5 A crystal structure functional core SCF bound extracellular ligand‐binding domains KIT. The reveals ‘wrapping’ SCF‐recognition mode by KIT, in which adopts bent conformation facilitate each its first three immunoglobulin (Ig)‐like interact SCF. Three surface epitopes on SCF, an extended loop, B C helices, N‐terminal segment, contact distinct domains, two undergoing large conformational changes upon binding. SCF/KIT complex unique RTK dimerization assembly, novel recognition between four‐helix bundle cytokines Ig‐family receptors. It serves as framework for understanding mechanisms RTKs.