10.1021/bi602353k.s002
Markos Pechlivanis
Markos
Pechlivanis
Rieke Ringel
Rieke
Ringel
Boriana Popkirova
Boriana
Popkirova
Juergen Kuhlmann
Juergen
Kuhlmann
Prenylation of Ras Facilitates hSOS1-Promoted Nucleotide Exchange, upon Ras
Binding to the Regulatory Site<sup>†</sup>
American Chemical Society
2007
Ras Binding
prenyl sensitivity
hSOS 1
hSOS 1. Farnesylation
GEF activity
Ras activation
feedback loop
nucleotide exchange
PH domain
lipid membranes
allosteric site
2007-05-08 00:00:00
Journal contribution
https://acs.figshare.com/articles/journal_contribution/Prenylation_of_Ras_Facilitates_hSOS1_Promoted_Nucleotide_Exchange_upon_Ras_Binding_to_the_Regulatory_Site_sup_sup_/3008902
The 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.