Hotspot Mutations in KIT Receptor Differentially Modulate Its Allosterically Coupled Conformational Dynamics: Impact on Activation and Drug Sensitivity

@inproceedings{Beauchne2014HotspotMI,
  title={Hotspot Mutations in KIT Receptor Differentially Modulate Its Allosterically Coupled Conformational Dynamics: Impact on Activation and Drug Sensitivity},
  author={Isaure Chauvot de Beauch{\^e}ne and Ariane Allain and Nicolas Panel and Elodie Laine and Alain Trouv{\'e} and Patrice Dubreuil and Luba Tchertanov},
  booktitle={PLoS Computational Biology},
  year={2014}
}
Receptor tyrosine kinase KIT controls many signal transduction pathways and represents a typical allosterically regulated protein. The mutation-induced deregulation of KIT activity impairs cellular physiological functions and causes serious human diseases. The impact of hotspots mutations (D816H/Y/N/V and V560G/D) localized in crucial regulatory segments, the juxtamembrane region (JMR) and the activation (A-) loop, on KIT internal dynamics was systematically studied by molecular dynamics… CONTINUE READING