Related Experiment Video

Updated: Mar 16, 2026

Light-mediated Reversible Modulation of the Mitogen-activated Protein Kinase Pathway during Cell Differentiation and Xenopus Embryonic Development
09:32

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

Published on: June 15, 2017

9.3K

MAPK kinase signalling dynamics regulate cell fate decisions and drug resistance

Nora Rauch1, Oleksii S Rukhlenko1, Walter Kolch2

  • 1Systems Biology Ireland, University College Dublin, Ireland.

Current Opinion in Structural Biology
|August 14, 2016
PubMed

Insights

The RAS/RAF/MEK/MAPK pathway

Area of Science:

  • Cellular signaling pathways
  • Molecular biology
  • Cancer research

Background:

  • The RAS/RAF/MEK/MAPK pathway is crucial for cell fate but its dynamics are complex.
  • Altered MAPK dynamics due to RAS/RAF/MEK mutations are linked to cancer and developmental disorders.
  • RAF/MEK inhibitors are developed for cancer but face side-effects and resistance.

Purpose of the Study:

  • To review the intricate dynamics of the RAS/RAF/MEK/MAPK pathway.
  • To explore how RAF dimerization contributes to drug resistance.
  • To discuss recent breakthroughs in overcoming resistance to RAF/MEK inhibitors.

Main Methods:

  • Literature review of modeling and experimental studies on MAPK dynamics.
  • Analysis of feedforward/feedback regulations and crosstalk in the MAPK pathway.
  • Examination of mechanisms of drug resistance, specifically RAF dimerization.

Main Results:

  • MAPK pathway dynamics are highly versatile, influenced by complex regulatory networks.
  • RAF dimerization is a key mechanism conferring resistance to RAF/MEK inhibitors.
  • Novel strategies are emerging to overcome RAF/MEK inhibitor resistance.

Conclusions:

  • Understanding MAPK pathway dynamics is essential for deciphering cell fate in normal and cancerous conditions.
  • Overcoming drug resistance, particularly through targeting RAF dimerization, is critical for effective cancer therapy.
  • Continued research into MAPK pathway regulation and resistance mechanisms promises improved therapeutic interventions.

More Related Videos

Intracellular Phosphoflow Cytometry of Acute Myeloid Leukemia Patient-Derived Xenotransplants07:38

Intracellular Phosphoflow Cytometry of Acute Myeloid Leukemia Patient-Derived Xenotransplants

Published on: June 6, 2025

893
A Method for Screening and Validation of Resistant Mutations Against Kinase Inhibitors12:40

A Method for Screening and Validation of Resistant Mutations Against Kinase Inhibitors

Published on: December 7, 2014

15.3K

Related Concept Videos

MAPK Signaling Cascades01:07

MAPK Signaling Cascades

Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...
9.0K
Interactions Between Signaling Pathways01:19

Interactions Between Signaling Pathways

Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
7.7K
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
5.0K
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

1.6K
PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

The mammalian target of rapamycin  (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1  (mTORC1) and mTOR complex 2  (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast,  mTORC2 consists of a...
6.1K
Mitogens and the Cell Cycle02:38

Mitogens and the Cell Cycle

Mitogens and their receptors play a crucial role in controlling the progression of the cell cycle. However, the loss of mitogenic control over cell division leads to tumor formation. Therefore, mitogens and mitogen receptors play an important role in cancer research. For instance, the epidermal growth factor (EGF) - a type of mitogen and its transmembrane receptor (EGFR), decides the fate of the cell's proliferation. When EGF binds to EGFR, a member of the ErbB family of tyrosine kinase...
8.3K