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Characterize Disease-related Mutants of RAF Family Kinases by Using a Set of Practical and Feasible Methods

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Published on: July 17, 2019

Ras/Raf dimerization model for activation of Raf kinase.

Marcela de Barros¹, Gregory Labrie¹, Carla Mattos¹

¹Department of Chemistry and Chemical Biology, Northeastern University, 360 Huntington Ave, Boston, MA 02115, USA.

Current Opinion in Structural Biology

|September 10, 2025

Summary

This summary is machine-generated.

Ras proteins dimerize to activate Raf, forming signaling platforms with Galectin. This mechanism explains Raf autoinhibition release and signal amplification, consistent with observed Ras stationary phases in cells.

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Area of Science:

Molecular biology
Cell signaling
Biochemistry

Background:

Ras proteins are key regulators of cell signaling pathways.
Raf kinases are crucial downstream effectors of Ras.
Previous models proposed Ras monomeric activation of Raf.

Purpose of the Study:

To review and reconcile mechanistic understanding of Raf activation.
To propose a model where Ras/Raf dimers are central to Raf activation.
To elucidate the role of signaling platforms in Raf activation and signal amplification.

Main Methods:

Review of existing literature and Nuclear Magnetic Resonance (NMR) data.
Analysis of Ras dimerization and its role in Raf activation.
Integration of nanocluster formation and Galectin involvement.

Main Results:

Ras activation of Raf is centered on Ras/Raf dimers, not Ras monomers.
Raf activation occurs within Ras nanoclusters, transitioning to dimers upon Raf binding.
A signaling platform involving Ras/Raf and Galectin dimers facilitates Raf autoinhibition release.

Conclusions:

Ras dimerization is critical for Raf activation and signal amplification.
The proposed signaling platform model explains Raf autoinhibition and intrinsically disordered region folding.
This model is consistent with experimental observations like Ras stationary phases in cells.