title: Nucleophosmin and nucleolin regulate K-Ras signaling.
abstract: Ras proteins are laterally segregated into transient nanoclusters on the plasma membrane, a property essential for high fidelity signal transduction through the MAPK pathway. From a proteomic screen we identified nucleophosmin (NPM) and nucleolin as two novel regulators of K-Ras plasma membrane interactions that in turn influence MAP Kinase signaling. NPM and nucleolin are predominately nucleolar proteins but also possess extra-nuclear functions. We showed that a subset of NPM and nucleolin localize to the inner leaflet of the plasma membrane and specifically interact with K-Ras but not H-Ras. This interaction is independent of the activation state of K-Ras, and stabilizes K-Ras membrane levels. NPM expression also increases the fraction of K-Ras in nanoclusters. The increase in clustered K-Ras-GTP enhances signaling through the MAPK pathway. Together these results identify NPM and nucleolin as a new class of K-Ras regulators that modulate signal transduction via the MAPK pathway.
authors.forename: Kerry L
authors.initials: KL
authors.lastname: Inder
authors.forename: Michelle M
authors.initials: MM
authors.lastname: Hill
authors.forename: John F
authors.initials: JF
authors.lastname: Hancock