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Related Concept Videos

NF-kB-dependent Signaling Pathway02:26

NF-kB-dependent Signaling Pathway

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
The heterodimer of NF-κB...
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...
NF-κB-dependent Signaling Pathway02:26

NF-κB-dependent Signaling Pathway

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
The heterodimer of NF-κB...
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.
Ras is a superfamily...
Regulation of Nuclear Protein Sorting01:45

Regulation of Nuclear Protein Sorting

Nuclear protein sorting regulates nucleus composition and gene expression, crucial for determining the fate of a eukaryotic cell. Hence, the entry and exit of molecules across the nuclear envelope is a tightly controlled process. Nuclear protein sorting can be inhibited by one of the following ways: 1) masking cargo signal sequences, 2) modifying the nuclear receptor's affinity for cargo, 3) controlling the nuclear pore size, 4) retaining the cargo during its transit to the cytosol or the...
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...

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Related Experiment Video

Updated: May 29, 2026

Using the E1A Minigene Tool to Study mRNA Splicing Changes
10:25

Using the E1A Minigene Tool to Study mRNA Splicing Changes

Published on: April 22, 2021

NF1 and SPRED1/2 cooperate through RAS-MAPK-independent functions.

Jillian M Silva1, Lizzeth Canche1, Alice Cheng1

  • 1Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA 94153.

Proceedings of the National Academy of Sciences of the United States of America
|May 27, 2026
PubMed
Summary
This summary is machine-generated.

Neurofibromin (NF1) and SPRED proteins regulate RAS-MAPK signaling independently of RAS. Their cooperation controls gene expression and impacts Neurofibromatosis type I patient cells, revealing novel therapeutic targets.

Keywords:
MAPKRASSPREDneurofibromin

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Validation of a Mouse Model to Disrupt LINC Complexes in a Cell-specific Manner
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Validation of a Mouse Model to Disrupt LINC Complexes in a Cell-specific Manner

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Related Experiment Videos

Last Updated: May 29, 2026

Using the E1A Minigene Tool to Study mRNA Splicing Changes
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Validation of a Mouse Model to Disrupt LINC Complexes in a Cell-specific Manner
09:02

Validation of a Mouse Model to Disrupt LINC Complexes in a Cell-specific Manner

Published on: December 10, 2015

Area of Science:

  • Molecular Biology
  • Cell Signaling
  • Genetics

Background:

  • Neurofibromin (NF1) negatively regulates the RAS-MAPK pathway through interaction with SPRED proteins.
  • While NF1's RAS GTPase-stimulating domain is known, other NF1 functions remain unclear.
  • The interplay between NF1 and SPRED1/2 in RAS-independent signaling requires further investigation.

Purpose of the Study:

  • To investigate the RAS-independent functions of NF1 and SPRED1/2.
  • To elucidate the cooperative mechanisms of NF1 and SPRED1/2 in cellular signaling.
  • To identify NF1-SPRED1/2-dependent gene signatures and their regulation.

Main Methods:

  • CRISPR-Cas9 gene editing in "RASless" mouse embryonic fibroblast (MEF) cell lines.
  • Utilized KRAS4b wild-type and oncogenic KRAS variants.
  • Transcriptome microarray analysis and validation in patient-derived Schwann cells.

Main Results:

  • Loss of SPRED1/2 phenocopied NF1 loss, highlighting their cooperative role in modulating MAPK-AKT signaling.
  • NF1 or SPRED1/2 loss suppressed RRAS and RRAS2 GTPases independently of RAS or AKT activation.
  • Identified specific RAS-independent gene signatures regulated by NF1-SPRED1/2 cooperation, also influenced by NF1's RAS-GTPase function.

Conclusions:

  • NF1 and SPRED1/2 cooperate to regulate RAS-independent signaling pathways.
  • This cooperation is uncoupled from canonical MAPK signaling and influences specific gene expression.
  • Findings provide insights into NF1's multifaceted roles beyond RAS regulation and potential therapeutic strategies for Neurofibromatosis type I.