Extracellular assembly and activation principles of oncogenic class III receptor tyrosine kinases.
Intracellular signalling cascades initiated by class III receptor tyrosine kinases (RTK-IIIs) and their cytokine ligands contribute to haematopoiesis and mesenchymal tissue development. They are also implicated in a wide range of inflammatory disorders and cancers. Recent snapshots of RTK-III ectodomains in complex with cognate cytokines have revealed timely insights into the structural determinants of RTK-III activation, evolution and pathology. Importantly, candidate 'driver' and 'passenger' mutations that have been identified in RTK-IIIs can now be collectively mapped for the first time to structural scaffolds of the corresponding RTK-III ectodomains. Such insights will generate a renewed interest in dissecting the mechanistic effects of such mutations and their therapeutic relevance.
Unit for Structural Biology, Laboratory for Protein Biochemistry and Biomolecular Engineering, Ghent University, K.L. Ledeganckstraat 35, 9000 Ghent, Belgium. kenneth.verstraete@ugent.be
Kenneth
K
Verstraete
Savvas N
SN
Savvides
D002471:Cell Transformation, Neoplastic; D016207:Cytokines / Q000378:metabolism*; D006410:Hematopoiesis / Q000502:physiology; D006801:Humans; D008024:Ligands; D009154:Mutation; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D015398:Signal Transduction
D016207:Cytokines; D008024:Ligands; D020794:Receptor Protein-Tyrosine Kinases