Jove
Visualize
Contact Us
JoVE
x logofacebook logolinkedin logoyoutube logo
ABOUT JoVE
OverviewLeadershipBlogJoVE Help Center
AUTHORS
Publishing ProcessEditorial BoardScope & PoliciesPeer ReviewFAQSubmit
LIBRARIANS
TestimonialsSubscriptionsAccessResourcesLibrary Advisory BoardFAQ
RESEARCH
JoVE JournalMethods CollectionsJoVE Encyclopedia of ExperimentsArchive
EDUCATION
JoVE CoreJoVE BusinessJoVE Science EducationJoVE Lab ManualFaculty Resource CenterFaculty Site
Terms & Conditions of Use
Privacy Policy
Policies

Related Concept Videos

Phosphorylation01:02

Phosphorylation

50.3K
The addition or removal of phosphate groups from proteins is the most common chemical modification that regulates cellular processes. These modifications can affect the structure, activity, stability, and localization of proteins within cells as well as their interactions with other proteins.
During phosphorylation, protein kinases transfer the terminal phosphate group of ATP to specific amino acid side chains of substrate proteins. Serine, threonine, and tyrosine are the most commonly...
50.3K
Amplifying Signals via Enzymatic Cascade01:22

Amplifying Signals via Enzymatic Cascade

8.5K
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...
8.5K
Protein Kinases and Phosphatases02:54

Protein Kinases and Phosphatases

13.1K
Proteins undergo chemical modifications that trigger changes in the charge, structure, and conformation of the proteins. Phosphorylation, acetylation, glycosylation, nitrosylation, ubiquitination, lipidation, methylation, and proteolysis are various protein modifications that regulate protein activity. Such modifications are usually enzyme-driven.
Protein kinases
Many proteins in the cell are regulated by phosphorylation, the addition of a phosphate group. A family of enzymes called kinases...
13.1K
ATP Energy Storage and Release01:31

ATP Energy Storage and Release

9.4K
ATP is a highly unstable molecule. Unless quickly used to perform work, ATP spontaneously dissociates into ADP and inorganic phosphate (Pi), and the free energy released during this process is lost as heat. The energy released by ATP hydrolysis is used to perform work inside the cell and depends on a strategy called energy coupling. Cells couple the exergonic reaction of ATP hydrolysis with endergonic reactions, allowing them to proceed.
One example of energy coupling using ATP involves a...
9.4K

You might also read

Related Articles

Articles linked to this work by shared authors, journal, and citation graph.

Sort by
Same author

A standardized workflow for kinetic metabolic model curation and dissemination.

PLoS computational biology·2026
Same author

Antimony 3: Extending human-readable model definitions for SBML Level 3 Core and Packages.

bioRxiv : the preprint server for biology·2026
Same author

From FAIR to CURE: guidelines for computational models of biological systems.

NPJ systems biology and applications·2026
Same author

Evaluating the limitations of Bayesian metabolic control analysis.

PLoS computational biology·2026
Same author

Verification and reproducible curation of the BioModels repository.

PLoS computational biology·2025
Same author

A Roadmap for the Future of Systems Biology in Cancer Research.

Cancer research·2025

Related Experiment Video

Updated: Jul 3, 2025

Oligopeptide Competition Assay for Phosphorylation Site Determination
09:16

Oligopeptide Competition Assay for Phosphorylation Site Determination

Published on: May 18, 2017

8.5K

First-order ultrasensitivity in phosphorylation cycles.

Michael A Kochen1, Joseph L Hellerstein2, Herbert M Sauro1

  • 1Department of Bioengineering, University of Washington, Seattle, WA 98105, USA.

Interface Focus
|February 12, 2024
PubMed
Summary

Cellular signal transduction pathways exhibit ultrasensitivity. New research reveals first-order ultrasensitivity in n-length cycles, which is robust against retroactivity, unlike zero-order ultrasensitivity.

Keywords:
cascadefirst-order ultrasensitivityfrequency responsephosphorylation cycle

More Related Videos

Identification of Cyclin-dependent Kinase 1 Specific Phosphorylation Sites by an In Vitro Kinase Assay
12:26

Identification of Cyclin-dependent Kinase 1 Specific Phosphorylation Sites by an In Vitro Kinase Assay

Published on: May 3, 2018

18.6K
An Optimized Single-Molecule Pull-Down Assay for Quantification of Protein Phosphorylation
07:45

An Optimized Single-Molecule Pull-Down Assay for Quantification of Protein Phosphorylation

Published on: June 6, 2022

2.9K

Related Experiment Videos

Last Updated: Jul 3, 2025

Oligopeptide Competition Assay for Phosphorylation Site Determination
09:16

Oligopeptide Competition Assay for Phosphorylation Site Determination

Published on: May 18, 2017

8.5K
Identification of Cyclin-dependent Kinase 1 Specific Phosphorylation Sites by an In Vitro Kinase Assay
12:26

Identification of Cyclin-dependent Kinase 1 Specific Phosphorylation Sites by an In Vitro Kinase Assay

Published on: May 3, 2018

18.6K
An Optimized Single-Molecule Pull-Down Assay for Quantification of Protein Phosphorylation
07:45

An Optimized Single-Molecule Pull-Down Assay for Quantification of Protein Phosphorylation

Published on: June 6, 2022

2.9K

Area of Science:

  • Biochemistry and Molecular Biology
  • Systems Biology
  • Cellular Dynamics

Background:

  • Cellular signal transduction relies on phosphorylation cycles.
  • These pathways form multi-layered cascades.
  • Understanding cascade sensitivity is crucial for cell function.

Purpose of the Study:

  • To investigate the sensitivity of single, double, and n-length phosphorylation cycles.
  • To analyze the impact of retroactivity on different ultrasensitivity types.
  • To explore methods for creating systems with broader sensitivity ranges.

Main Methods:

  • Frequency analysis to compute cascade bandwidth and assess noise filtering.
  • Mathematical modeling to analyze ultrasensitivity in various cycle lengths.
  • Comparison of zero-order ultrasensitivity (ZOU) and first-order ultrasensitivity (FOU).

Main Results:

  • Confirmed cascades act as noise filters via bandwidth computation.
  • Identified first-order ultrasensitivity (FOU) in n-length cycles, independent of the zero-order regime.
  • Demonstrated that FOU is immune to retroactivity, unlike ZOU.
  • Showed that ZOU in double cycles offers only a modest increase over single cycles.

Conclusions:

  • First-order ultrasensitivity provides a novel mechanism for signal amplification in cellular pathways.
  • Blending ZOU and FOU can yield systems with enhanced and tunable sensitivity.
  • Double cycles may have evolved for amplification despite retroactivity challenges.