Related Experiment Video
Updated: Jun 18, 2026

Characterize Disease-related Mutants of RAF Family Kinases by Using a Set of Practical and Feasible Methods
Published on: July 17, 2019
From autoinhibition to inhibition in trans: the Raf-1 regulatory domain inhibits Rok-alpha kinase activity
Théodora Niault1, Izabela Sobczak, Katrin Meissl
1Max F. Perutz Laboratories, Center for Molecular Biology, University of Vienna, 1030 Vienna, Austria.
None:
The activity of Raf-1 and Rok-alpha kinases is regulated by intramolecular binding of the regulatory region to the kinase domain. Autoinhibition is relieved upon binding to the small guanosine triphosphatases Ras and Rho. Downstream of Ras, Raf-1 promotes migration and tumorigenesis by antagonizing Rok-alpha, but the underlying mechanism is unknown. In this study, we show that Rok-alpha inhibition by Raf-1 relies on an intermolecular interaction between the Rok-alpha kinase domain and the cysteine-rich Raf-1 regulatory domain (Raf-1reg), which is similar to Rok-alpha's own autoinhibitory region. Thus, Raf-1 mediates Rok-alpha inhibition in trans, which is a new concept in kinase regulation. This mechanism is physiologically relevant because Raf-1reg is sufficient to rescue all Rok-alpha-dependent defects of Raf-1-deficient cells. Downstream of Ras and Rho, the Raf-1-Rok-alpha interaction represents a novel paradigm of pathway cross talk that contributes to tumorigenesis and cell motility.
More Related Videos
06:44Bioluminescence Resonance Energy Transfer (BRET)-Based Assay for Measuring Interactions of CRAF with 14-3-3 Proteins in Live Cells
Published on: March 1, 2024
09:32Light-mediated Reversible Modulation of the Mitogen-activated Protein Kinase Pathway during Cell Differentiation and Xenopus Embryonic Development
Published on: June 15, 2017
Related Concept Videos
MAPK Signaling Cascades
PI3K/mTOR/AKT Signaling Pathway
The JAK-STAT Signaling Pathway
The Ras Gene
Ras is a superfamily...
Small GTPases - Ras and Rho
Three regulatory proteins control their activity:
mTOR Signaling and Cancer Progression
The mTOR pathway or the...