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Related Concept Videos

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...
Amplifying Signals via Enzymatic Cascade01:22

Amplifying Signals via Enzymatic Cascade

When a ligand binds to a cell-surface receptor, the receptor's intracellular domain changes shape, which may either activate its enzyme function or allow its binding to other molecules. The initial signal is amplified by most signal transduction pathways. This means that a single ligand molecule can activate multiple molecules of a downstream target. Proteins that relay a signal are most commonly phosphorylated at one or more sites, activating or inactivating the protein. Kinases catalyze the...
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...
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...
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.
Three regulatory proteins control their activity:
The JAK-STAT Signaling Pathway01:20

The JAK-STAT Signaling Pathway

Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as  SH2...

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Related Experiment Video

Updated: Jun 27, 2026

Identification of EGFR and RAS Inhibitors using Caenorhabditis elegans
08:12

Identification of EGFR and RAS Inhibitors using Caenorhabditis elegans

Published on: October 5, 2020

Signaling threshold regulation by the Ras effector IMP.

Sharon A Matheny1, Michael A White

  • 1Zimmer Biologics, Austin, Texas 78729, USA.

The Journal of Biological Chemistry
|December 19, 2008
PubMed
Summary

Impedes mitogenic signal propagation (IMP) protein regulates the Raf-MEK-ERK pathway by controlling KSR1 complex assembly. This mechanism modulates cellular sensitivity to stimuli, acting as a crucial threshold modulator.

Area of Science:

  • Molecular Biology
  • Cell Signaling
  • Biochemistry

Background:

  • The Ras-Raf-MEK-ERK pathway is critical for cell growth and proliferation.
  • Impedes mitogenic signal propagation (IMP) is an E3 ligase that negatively regulates this pathway.
  • Understanding IMP's role is key to deciphering pathway sensitivity and threshold modulation.

Purpose of the Study:

  • To elucidate the molecular mechanisms by which IMP inhibits the Raf-MEK-ERK pathway.
  • To investigate IMP's interaction with KSR1 and its role in complex assembly.
  • To define IMP's function as a threshold modulator in signal transduction.

Main Methods:

  • Biochemical assays to study protein interactions and complex formation.
  • Analysis of autoubiquitination and its effect on IMP function.

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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

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Last Updated: Jun 27, 2026

Identification of EGFR and RAS Inhibitors using Caenorhabditis elegans
08:12

Identification of EGFR and RAS Inhibitors using Caenorhabditis elegans

Published on: October 5, 2020

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

  • Investigating the impact of IMP on Raf-MEK and KSR1 oligomerization.

    • Main Results:

    • IMP concentration is regulated by Ras via autoubiquitination, enabling Raf-MEK complex assembly.
    • IMP inhibits pathway activation by inactivating KSR, a scaffold protein.
    • IMP disrupts KSR1 homo-oligomerization and c-Raf-B-Raf hetero-oligomerization, limiting functional complex assembly.

    Conclusions:

    • IMP acts as a steady-state resistor in the Raf-MEK-ERK pathway.
    • IMP functions as a threshold modulator, controlling cascade sensitivity to stimuli.
    • IMP limits the assembly of functional KSR1-dependent Raf-MEK complexes, thereby regulating signal propagation.