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

Assembly of Signaling Complexes01:30

Assembly of Signaling Complexes

6.5K
Multiprotein signaling complexes are formed in a dynamic process involving protein-protein interactions at the cytoplasmic domain of transmembrane receptors or enzymatic and non-enzymatic proteins associated with the receptor. These complexes ensure the activation and propagation of intracellular signals that regulate cell functions.
Interaction domains in cell signaling
Interaction domains recognize exposed features of their binding partners containing post-translationally modified sequences,...
6.5K
Signal Transduction: Overview01:26

Signal Transduction: Overview

11.4K
Cells respond to many types of information, often through receptor proteins positioned on the membrane. They respond to chemical signals, such as hormones, neurotransmitters, and other signaling molecules, initiating a series of molecular reactions to produce an appropriate response. This is called signal transduction. Cells also coordinate different responses elicited by the same signaling molecule via mediators, allowing molecular cross-talk.
Typically, signal transduction involves three...
11.4K
Intracellular Signaling Cascades01:24

Intracellular Signaling Cascades

53.3K
Once a ligand binds to a receptor, the signal is transmitted through the membrane and into the cytoplasm. The continuation of a signal in this manner is called signal transduction. Signal transduction only occurs with cell-surface receptors, which cannot interact with most components of the cell, such as DNA. Only internal receptors can interact directly with DNA in the nucleus to initiate protein synthesis. When a ligand binds to its receptor, conformational changes occur that affect the...
53.3K
Interactions Between Signaling Pathways01:19

Interactions Between Signaling Pathways

7.2K
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...
7.2K
Amplifying Signals via Second Messengers01:15

Amplifying Signals via Second Messengers

8.5K
Many receptor binding ligands are hydrophilic; they do not cross the cell membrane but bind to cell-surface receptors. Thus, their message must be relayed by second messengers present in the cell cytoplasm. There are several second messenger pathways, each with its own way of relaying information. For example, the G protein-coupled receptors can activate both phosphoinositol and cyclic AMP (cAMP) second messenger pathways. The phosphoinositol pathway is active when the receptor induces...
8.5K
Amplifying Signals via Enzymatic Cascade01:22

Amplifying Signals via Enzymatic Cascade

17.5K
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...
17.5K

You might also read

Related Articles

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

Sort by
Same author

A molecular switch in mouse CD1d modulates natural killer T cell activation by α-galactosylsphingamides.

The Journal of biological chemistry·2019
Same author

Structure of human cytomegalovirus UL144, an HVEM orthologue, bound to the B and T cell lymphocyte attenuator.

The Journal of biological chemistry·2019
Same author

Crystal structure of the m4-1BB/4-1BBL complex reveals an unusual dimeric ligand that undergoes structural changes upon 4-1BB receptor binding.

The Journal of biological chemistry·2018
Same author

Crystal structures of the human 4-1BB receptor bound to its ligand 4-1BBL reveal covalent receptor dimerization as a potential signaling amplifier.

The Journal of biological chemistry·2018
Same author

Crystal structure of murine 4-1BB and its interaction with 4-1BBL support a role for galectin-9 in 4-1BB signaling.

The Journal of biological chemistry·2017
Same author

Crystal structure of Qa-1a with bound Qa-1 determinant modifier peptide.

PloS one·2017
Same journal

Correction: Characterization of Mast2 kinase defines structural features, regulation, and substrates.

The Journal of biological chemistry·2026
Same journal

Isotope-Edited ESEEM: A New Method for Probing Copper Binding Sites in Neurodegenerative Proteins.

The Journal of biological chemistry·2026
Same journal

Introduction to the Thematic Review Series on Intracellular Protein Degradation. The ubiquitous biology of intracellular protein degradation: a tribute to Alfred L. ("Fred") Goldberg.

The Journal of biological chemistry·2026
Same journal

Correction: Aromatic residue-rich amino-terminal segments of temporin L self-assemble into collagen-mimetic peptides with cell-adhesion properties.

The Journal of biological chemistry·2026
Same journal

YhbO is a DJ-1 family glyoxalase and α-oxoaldehyde hydratase that confers resistance to reactive carbonyl stress (112).

The Journal of biological chemistry·2026
Same journal

ARMH3 acts as a central scaffold at the Golgi/TGN through interactions with Arl5, GBF1, and PI4KB.

The Journal of biological chemistry·2026
See all related articles

Related Experiment Video

Updated: Jan 19, 2026

Dissecting Multi-protein Signaling Complexes by Bimolecular Complementation Affinity Purification BiCAP
06:45

Dissecting Multi-protein Signaling Complexes by Bimolecular Complementation Affinity Purification BiCAP

Published on: June 15, 2018

7.9K

Catching a complex for optimal signaling.

Dirk M Zajonc1

  • 1Cancer Immunology Discovery Oncology R&D Group, Pfizer Inc., San Diego, California 92121 Dirk.Zajonc@pfizer.com.

The Journal of Biological Chemistry
|September 22, 2019
PubMed
Summary
This summary is machine-generated.

Researchers developed a novel single-chain variable fragment (scFv) "stapler" to precisely activate cell surface receptors. This method ensures accurate receptor dimerization for signaling, even without natural ligands.

More Related Videos

Mimicking the Function of Signaling Proteins: Toward Artificial Signal Transduction Therapy
12:24

Mimicking the Function of Signaling Proteins: Toward Artificial Signal Transduction Therapy

Published on: September 29, 2016

7.4K
Real-time Live Imaging of T-cell Signaling Complex Formation
10:31

Real-time Live Imaging of T-cell Signaling Complex Formation

Published on: June 23, 2013

14.5K

Related Experiment Videos

Last Updated: Jan 19, 2026

Dissecting Multi-protein Signaling Complexes by Bimolecular Complementation Affinity Purification BiCAP
06:45

Dissecting Multi-protein Signaling Complexes by Bimolecular Complementation Affinity Purification BiCAP

Published on: June 15, 2018

7.9K
Mimicking the Function of Signaling Proteins: Toward Artificial Signal Transduction Therapy
12:24

Mimicking the Function of Signaling Proteins: Toward Artificial Signal Transduction Therapy

Published on: September 29, 2016

7.4K
Real-time Live Imaging of T-cell Signaling Complex Formation
10:31

Real-time Live Imaging of T-cell Signaling Complex Formation

Published on: June 23, 2013

14.5K

Area of Science:

  • Immunology
  • Molecular Biology
  • Structural Biology

Background:

  • Agonistic antibodies can dimerize cell surface receptors to trigger signaling pathways.
  • Accurate receptor activation requires antibodies to precisely mimic the native dimeric state.
  • Existing methods may not perfectly recapitulate native receptor conformations.

Purpose of the Study:

  • To develop a high-fidelity method for activating cell surface receptors using engineered antibodies.
  • To create a tool that selectively targets and dimerizes specific receptor complexes.
  • To enable receptor signaling in the absence of endogenous ligands.

Main Methods:

  • Engineered a monovalent single-chain variable fragment (scFv) termed a "stapler."
  • Selected for antibodies that bind the IL-4Rα/γc heterodimeric complex in its native signaling conformation.
  • Utilized the scFv to bind at the receptor dimerization interface.

Main Results:

  • Developed a stapler scFv that binds the IL-4Rα/γc heterodimeric complex.
  • The stapler successfully recapitulates the native dimeric state for receptor activation.
  • Demonstrated a method for precise receptor dimerization and signaling.

Conclusions:

  • The stapler approach provides a powerful and specific method for receptor activation.
  • This technique can be applied to various homo- and heterodimeric receptors.
  • Enables controlled receptor signaling, particularly when endogenous ligands are absent.