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Related Concept Videos

Rab Proteins01:14

Rab Proteins

Rab proteins constitute the largest family of monomeric GTPases, of which 70 members are present in humans. Rab proteins and their effectors regulate consecutive stages of vesicle transport such as vesicle transport, docking, and fusion to the correct recipient membrane.
Rab proteins switch between a cytosolic, GDP-bound inactive state and a membrane-anchored, GTP-bound active state. By themselves, Rabs show slow rates of GDP/GTP exchange and GTP hydrolysis. Thus, Rab proteins are considered...
The Ras Gene02:38

The Ras Gene

The Ras-gene-encoded proteins are regulators of signaling pathways controlling cell proliferation, differentiation, or cell survival. The Ras-gene family in humans constitutes three primary members—the HRas, NRas, and KRas. These genes code for four functionally distinct yet closely related proteins—the HRas, NRas, KRas4A, and KRas4B. The involvement of mutant Ras genes in human cancer was first discovered in 1982 and is among the most common causes of human tumorigenesis.
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Interactions Between Signaling Pathways01:19

Interactions Between Signaling Pathways

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Convergence and divergence, and cross-talk between signaling pathways
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Receptor Tyrosine Kinases01:26

Receptor Tyrosine Kinases

Receptor tyrosine kinases or RTKs are membrane-bound receptors that phosphorylate specific tyrosine on protein substrates. RTKs regulate cellular growth, differentiation, survival, and migration. They contain an extracellular ligand binding domain, a transmembrane domain, and a cytosolic tail with intrinsic kinase activity. Several extracellular signaling molecules activate RTKs in one or more ways and relay the signal downstream. Ligands such as platelet-derived growth factor (PDGF) or...
Small GTPases - Ras and Rho01:24

Small GTPases - Ras and Rho

Ras and Rho are small monomeric GTPases that act downstream of receptor tyrosine kinase (RTK) and regulate various cellular processes. These GTPases switch between active and inactive states by binding to guanine nucleotides.
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MAPK Signaling Cascades01:07

MAPK Signaling Cascades

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Related Experiment Video

Updated: May 21, 2026

Light-mediated Reversible Modulation of the Mitogen-activated Protein Kinase Pathway during Cell Differentiation and Xenopus Embryonic Development
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Light-mediated Reversible Modulation of the Mitogen-activated Protein Kinase Pathway during Cell Differentiation and Xenopus Embryonic Development

Published on: June 15, 2017

A dimerization-dependent mechanism drives RAF catalytic activation.

Thanashan Rajakulendran1, Malha Sahmi, Martin Lefrançois

  • 1Centre for Systems Biology, Samuel Lunenfeld Research Institute, Toronto, Ontario M5G 1X5, Canada.

Nature
|September 4, 2009
PubMed
Summary
This summary is machine-generated.

RAF kinases are activated through side-to-side dimerization, a process involving KSR and crucial for BRAF-driven cancers. Targeting this dimer interface offers a potential therapeutic strategy for tumorigenesis.

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Bioluminescence Resonance Energy Transfer (BRET)-Based Assay for Measuring Interactions of CRAF with 14-3-3 Proteins in Live Cells

Published on: March 1, 2024

Area of Science:

  • Cellular signaling pathways
  • Molecular biology
  • Cancer research

Background:

  • The extracellular signal-regulated kinase (ERK) pathway regulates cell growth, differentiation, and survival.
  • Dysregulation of the ERK pathway, particularly via mutations in RAF kinases like BRAF, is implicated in numerous human cancers.
  • Understanding RAF kinase activation mechanisms is critical for developing targeted cancer therapies.

Purpose of the Study:

  • To elucidate the molecular mechanism of RAF kinase activation.
  • To investigate the role of RAF dimerization in pathway regulation.
  • To identify potential therapeutic targets for BRAF-mutant cancers.

Main Methods:

  • Utilized Drosophila Schneider S2 cells for experimental analysis.
  • Investigated RAF kinase domain dimerization.
  • Examined the interaction between RAF and KSR (kinase suppressor of Ras).

Main Results:

  • Demonstrated that RAF catalytic function is regulated by a specific side-to-side dimer formation of its kinase domain.
  • Showed that KSR forms heterodimers with RAF, triggering RAF activation.
  • Confirmed that RAF side-to-side dimer formation is essential for oncogenic BRAF signaling and identified a mutation promoting this dimerization.

Conclusions:

  • RAF activation is controlled by side-to-side dimerization of its kinase domain.
  • KSR acts as a crucial regulator of RAF activation through heterodimerization.
  • The RAF side-to-side dimer interface represents a promising therapeutic target for BRAF-dependent cancers.