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

MAPK Signaling Cascades01:07

MAPK Signaling Cascades

5.7K
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...
5.7K
PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

3.7K
The mammalian target of rapamycin  (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1  (mTORC1) and mTOR complex 2  (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast,  mTORC2 consists of a...
3.7K
Receptor Tyrosine Kinases01:26

Receptor Tyrosine Kinases

13.2K
Receptor tyrosine kinases or RTKs are membrane-bound receptors that phosphorylate specific tyrosine on protein substrates. RTKs regulate cellular growth, differentiation, survival, and migration. They contain an extracellular ligand binding domain, a transmembrane domain, and a cytosolic tail with intrinsic kinase activity. Several extracellular signaling molecules activate RTKs in one or more ways and relay the signal downstream. Ligands such as platelet-derived growth factor (PDGF) or...
13.2K
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
Interactions Between Signaling Pathways01:19

Interactions Between Signaling Pathways

6.3K
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...
6.3K
Calmodulin-dependent Signaling01:16

Calmodulin-dependent Signaling

5.2K
Calmodulin (CaM) is a calcium-binding protein in eukaryotes that controls various calcium-regulated cellular processes. It has four calcium-binding sites that bind calcium to form the calcium-calmodulin ( Ca2+-CaM) complex. GPCR stimulation increases the calcium levels in the cells that bind to CaM and induces a conformational change.
The Ca2+-CaM complex does not have enzymatic activity by itself. Instead, the complex binds downstream target proteins, including membrane proteins or enzymes,...
5.2K

You might also read

Related Articles

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

Sort by
Same author

Riding toward Selectivity: Optimization of Covalent 7-Azaindole-Based BMX Kinase Inhibitors.

Journal of medicinal chemistry·2026
Same author

USP22 is a novel vulnerability regulating MEIS1 protein abundance and gene transcription in KMT2Ar acute leukemia.

Blood·2026
Same author

AURORA A interacts with DICER and SETD2 to promote S-phase progression.

EMBO reports·2026
Same author

On the Scope of DCAF1-Recruiting PROTACs Degrading Protein Kinases.

Journal of medicinal chemistry·2026
Same author

The structural basis for LRRK2's activation and autoinhibition.

bioRxiv : the preprint server for biology·2026
Same author

First Structure-Activity-Relationship Study of Potent G2A Antagonists.

Journal of medicinal chemistry·2026

Related Experiment Video

Updated: Jul 27, 2025

Deciphering the Structural Effects of Activating EGFR Somatic Mutations with Molecular Dynamics Simulation
15:05

Deciphering the Structural Effects of Activating EGFR Somatic Mutations with Molecular Dynamics Simulation

Published on: May 20, 2020

8.7K

Mutation in the Common Docking Domain Affects MAP Kinase ERK2 Catalysis and Stability.

Leonore Novak1, Maria Petrosino2, Alessandra Pasquo3

  • 1Dipartimento di Scienze Biochimiche "A. Rossi Fanelli", Sapienza University of Rome, 00185 Rome, Italy.

Cancers
|June 10, 2023
PubMed
Summary

Mutations in the ERK2 docking site impact its function and stability. This study analyzes how these changes affect cancer-related signaling pathways, revealing potential therapeutic targets.

Keywords:
ERK2MAP kinaseMAPK1cancer mutations and protein structure alterationsmutationprotein stabilitysingle nucleotide variant

More Related Videos

Assaying Protein Kinase Activity with Radiolabeled ATP
08:05

Assaying Protein Kinase Activity with Radiolabeled ATP

Published on: May 26, 2017

18.5K
Characterize Disease-related Mutants of RAF Family Kinases by Using a Set of Practical and Feasible Methods
07:49

Characterize Disease-related Mutants of RAF Family Kinases by Using a Set of Practical and Feasible Methods

Published on: July 17, 2019

6.1K

Related Experiment Videos

Last Updated: Jul 27, 2025

Deciphering the Structural Effects of Activating EGFR Somatic Mutations with Molecular Dynamics Simulation
15:05

Deciphering the Structural Effects of Activating EGFR Somatic Mutations with Molecular Dynamics Simulation

Published on: May 20, 2020

8.7K
Assaying Protein Kinase Activity with Radiolabeled ATP
08:05

Assaying Protein Kinase Activity with Radiolabeled ATP

Published on: May 26, 2017

18.5K
Characterize Disease-related Mutants of RAF Family Kinases by Using a Set of Practical and Feasible Methods
07:49

Characterize Disease-related Mutants of RAF Family Kinases by Using a Set of Practical and Feasible Methods

Published on: July 17, 2019

6.1K

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Cellular Signaling

Background:

  • Extracellular-signal-regulated kinase 2 (ERK2) is a key mitogen-activated protein kinase (MAPK) in the Ras-Raf-MEK-ERK pathway.
  • ERK2 signaling is crucial for cellular processes and its deregulation is linked to human diseases, notably cancer.
  • The common docking site (CD-site) of ERK2 is vital for substrate and regulator interactions.

Purpose of the Study:

  • To conduct a comprehensive biophysical analysis of wild-type and variant human ERK2 (non-phosphorylated and phosphorylated).
  • To investigate the impact of missense mutations in the ERK2 CD-site on its structure, function, and stability.
  • To understand how point mutations affect the ERK2 structure-function relationship in the context of cancer.

Main Methods:

  • Purification of recombinant human non-phosphorylated (NP-) and phosphorylated (P-) ERK2 wild-type and missense variants.
  • Comprehensive biophysical analysis including structural, functional, and stability assays.
  • Characterization of variants located in the common docking site (CD-site).

Main Results:

  • Most P-ERK2 variants in the CD-site exhibited reduced catalytic efficiency.
  • Specific variants (P-ERK2 D321E, D321N, D321V, E322K) showed altered thermodynamic stability.
  • Thermal stability was decreased in NP-ERK2 and P-ERK2 variants (D321E, D321G, E322K) compared to wild-type.

Conclusions:

  • Single residue mutations in the ERK2 CD-site can induce local structural changes.
  • These structural alterations lead to changes in global ERK2 stability and catalytic activity.
  • Understanding these mutations' effects is crucial for deciphering ERK2's role in disease and developing targeted therapies.