bi602353k_si_002.pdf (1.72 MB)
Prenylation of Ras Facilitates hSOS1-Promoted Nucleotide Exchange, upon Ras Binding to the Regulatory Site†
journal contribution
posted on 2007-05-08, 00:00 authored by Markos Pechlivanis, Rieke Ringel, Boriana Popkirova, Juergen KuhlmannThe oncoprotein Ras is anchored in lipid membranes due to its C-terminal lipid modification.
The ubiquitously expressed Ras nucleotide exchange-factor hSOS1 promotes nucleotide exchange and
thus Ras activation. This reaction is enhanced by a positive feedback loop whereby activated Ras binds
to an allosteric site of SOS to enhance GEF activity. Here we present biochemical data showing that
prenylation of both active site bound and allosterically bound N-Ras is required for efficient hSOS1-promoted nucleotide exchange. Our results indicate that prenyl sensitivity of the allosteric feedback-activation is mediated by the PH domain of hSOS1. Farnesylation of Ras thereby allows hSOS1 to bind
even GDP-loaded allosteric regulator to maintain basal hSOS1-activity.