Mechanistic insights into the recruitment of RAF kinase to the plasma membrane by KRAS

Abstract

KRAS is a small GTPase that is frequently mutated in human cancers, particularly pancreatic, colorectal and lung cancer. Engagement of mitogens with transmembrane receptor tyrosine kinases result in the activation of KRAS from an inactive GDP to active GTP bound state. Localized on the inner leaflet of the plasma membrane, active KRAS-GTP serves to recruit RAF kinase to the membrane where it undergoes activation. Oncogenic mutations lock KRAS in the active GTP state resulting in dysregulated cellular growth and proliferation.