KRAS Prenylation is required for Bivalent Binding with CaM in a Nucleotide Independent Manner (Biophysical Journal)

Deregulation of KRAS4b signaling pathway has been implicated in 30% of all cancers. Membrane localization of KRAS4b is an essential step for initiation of the downstream signaling cascades that guides various cellular mechanisms. KRAS4b plasma membrane (PM) binding is mediated by insertion of a prenylated moiety that is attached to the terminal carboxy-methylated cysteine, in addition to electrostatic interactions of its positively charged hypervariable region (HVR) with anionic lipids. Calmodulin has been suggested to selectively bind KRAS4b to act as a negative regulator of the RAS/MAPK signaling pathway by displacing KRAS4b from the membrane.