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Related Concept Videos

The Ras Gene02:38

The Ras Gene

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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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Interactions Between Signaling Pathways01:19

Interactions Between Signaling Pathways

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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.
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...
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MAPK Signaling Cascades01:07

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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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NF-κB-dependent Signaling Pathway02:26

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The transcription factor NF-κB was discovered in 1986 in the lab of Nobel laureate Professor David Baltimore, for its interaction with the immunoglobulin light chain enhancer in B-cells. After more than three decades of study, it is now evident that NF-κB regulates the expression of over 100 genes. Most of these genes play an essential role in the innate and adaptive immune responses as well as the inflammatory responses of animals.
NF-κB-dependent Signaling Mechanism
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Small GTPases - Ras and Rho01:24

Small GTPases - Ras and Rho

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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.
Three regulatory proteins control their activity:
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TGF - β Signaling Pathway01:16

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The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors...
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Related Experiment Video

Updated: May 2, 2026

Protocol for the Differentiation of Human Induced Pluripotent Stem Cells into Mixed Cultures of Neurons and Glia for Neurotoxicity Testing
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NRAS isoforms differentially affect downstream pathways, cell growth, and cell transformation.

Ann-Kathrin Eisfeld1, Sebastian Schwind, Kevin W Hoag

  • 1The Ohio State University Comprehensive Cancer Center, Columbus, OH 43210.

Proceedings of the National Academy of Sciences of the United States of America
|March 4, 2014
PubMed
Summary
This summary is machine-generated.

Researchers discovered four new NRAS isoforms, expanding the known NRAS variants. These novel isoforms exhibit distinct expression patterns and functional roles in cell signaling, offering new insights into oncogene research.

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Area of Science:

  • Molecular Biology
  • Oncology
  • Cellular Signaling

Background:

  • The NRAS (Neuroblastoma RAS viral oncogene homolog) gene encodes a small GTPase crucial for cell growth, differentiation, and survival.
  • NRAS acts as a central regulator in signal transduction pathways, making it a key focus in cancer research.

Purpose of the Study:

  • To identify and characterize novel naturally occurring isoforms of NRAS beyond the canonical isoform.
  • To investigate the expression patterns and functional differences of these newly identified NRAS isoforms in human malignancies.

Main Methods:

  • Isoform identification through molecular cloning and sequencing.
  • Expression analysis using quantitative PCR and Western blotting across various human cancer types and normal tissues.
  • Functional assays to determine subcellular localization, downstream target binding affinities, and effects on cell proliferation and transformation.

Main Results:

  • Four novel NRAS isoforms (isoforms 2-5) were identified, in addition to the canonical isoform 1.
  • Distinct expression patterns of these isoforms were observed in different human malignancies compared to normal tissues.
  • Novel isoforms displayed varied subcellular localization (nucleus and cytoplasm) and differential regulation of the RAS signaling pathway.
  • Forced expression of isoform 5, a short peptide, significantly increased cell proliferation and induced cellular transformation via NRAS targets.

Conclusions:

  • The discovery of novel NRAS isoforms significantly expands our understanding of NRAS biology.
  • These isoforms exhibit unique expression profiles and functional activities, suggesting isoform-specific roles in cancer development.
  • Further research into these NRAS isoforms may reveal new therapeutic targets for NRAS-driven cancers.