PMID: 17255936

 

    Legend: Gene, Sites

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

Abstract :

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

Output (sent_index, trigger, protein, sugar, site):

Output(Part-Of) (sent_index, protein, site):

• 3. KIT, domains
• 5. -, domains
• 5. -, epitopes
• 5. KIT, domains
• 5. SCF, epitopes

*Output_Site_Fusion* (sent_index, protein, sugar, site):

 

Protein	NCBI ID	SENTENCE INDEX
Stem cell factor	4254	1
SCF	4254	1,3,4,5,6
KIT receptor	3815	1
stem cell factor	4254	0
KIT	3815	0,2,3,4,5,6