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Related Concept Videos

MAPK Signaling Cascades01:07

MAPK Signaling Cascades

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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...
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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.
Ras is a...
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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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Multicellular organisms contain a variety of structurally and functionally distinct cell types, but the DNA in all the cells originated from the same parent cells. The differences in the cells can be attributed to the differential gene expression. Liver cells, whose functions include detoxification of blood, production of bile to metabolize fats, and synthesis of proteins essential for metabolism, must express a specific set of genes to perform their functions. Gene expression also varies with...
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Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the...
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Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
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Updated: Nov 26, 2025

Characterize Disease-related Mutants of RAF Family Kinases by Using a Set of Practical and Feasible Methods
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Exploiting codon usage identifies intensity-specific modifiers of Ras/MAPK signaling in vivo.

Jessica K Sawyer1, Zahra Kabiri1, Ruth A Montague1

  • 1Department of Pharmacology & Cancer Biology, Duke University School of Medicine, Durham, North Carolina, United States of America.

Plos Genetics
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Altering codon usage in Drosophila identified ribosomal gene RpS21 as a regulator of Ras/MAPK signaling. RpS21 specifically influences weak Ras-driven phenotypes, revealing new signaling control mechanisms.

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Area of Science:

  • Molecular Biology
  • Genetics
  • Cell Signaling

Background:

  • Signal transduction pathways, like the Ras/mitogen-activated-protein-kinase (MAPK) pathway, are crucial for biological processes and exhibit complex regulation.
  • Understanding the fine-tuning of these pathways is essential for deciphering cellular functions and disease mechanisms.

Purpose of the Study:

  • To explore codon usage manipulation as a novel strategy to identify context-specific regulators of signaling pathways.
  • To screen the Drosophila genome for modifiers of Ras-driven eye phenotypes, distinguishing between weak and strong signaling outputs.

Main Methods:

  • A forward genetic screen in Drosophila was performed using codon usage alteration to modulate Ras/MAPK signaling.
  • Phenotypic analysis of Ras-driven eye development was used to identify genetic modifiers.
  • Positional cloning was employed to map the genetic locus of a significant modifier.

Main Results:

  • The screen identified genomic regions not previously associated with Ras phenotypic modification.
  • A ribosomal protein gene, RpS21, was identified as a key modifier.
  • RpS21 was shown to preferentially influence weak Ras/MAPK signaling outputs across multiple experimental contexts.

Conclusions:

  • Codon usage manipulation is a viable approach for discovering novel, output-specific regulators of signaling pathways.
  • RpS21 acts as an in vivo regulator of Ras/MAPK signaling, particularly impacting weaker signaling outputs.