Related Experiment Video

Updated: Jun 10, 2026

Studying Cell Cycle-regulated Gene Expression by Two Complementary Cell Synchronization Protocols
12:02

Studying Cell Cycle-regulated Gene Expression by Two Complementary Cell Synchronization Protocols

Published on: June 6, 2017

Alternative ERK5 regulation by phosphorylation during the cell cycle

Francisco A Iñesta-Vaquera1, David G Campbell, Cathy Tournier

  • 1Departamento de Inmunología y Oncología, Centro Nacional de Biotecnología/CSIC, Campus de Cantoblanco, E-28049 Madrid, Spain.

Cellular Signalling
|July 30, 2010
PubMed

Insights

Mitotic regulation of ERK5 (Extracellular signal-regulated kinase 5) involves novel phosphorylation sites, distinct from its activation motif. This cyclin-dependent kinase (CDK)-dependent process inhibits ERK5 activity and controls its nuclear translocation during cell division.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • Extracellular signal-regulated kinase 5 (ERK5) is a mitogen-activated protein kinase (MAPK) crucial for cell proliferation, survival, differentiation, and stress response.
  • ERK5 regulates cell cycle progression, particularly G2/M phase transition and mitotic entry.
  • The precise mechanisms governing ERK5 regulation during mitosis remain largely unelucidated.

Purpose of the Study:

  • To investigate the molecular mechanisms of ERK5 regulation during mitosis.
  • To identify specific phosphorylation sites and regulatory kinases involved in mitotic ERK5 control.
  • To determine the functional consequences of mitotic ERK5 phosphorylation on its activity and localization.

Main Methods:

  • Phosphoproteomic analysis to identify mitotic phosphorylation sites on ERK5.
  • Site-directed mutagenesis to assess the functional significance of identified phosphorylation residues.
  • In vitro kinase assays to determine the dependency on specific kinases like MEK5 and CDK.
  • Cellular localization studies to track ERK5 shuttling between cytoplasm and nucleus.

Main Results:

  • ERK5 undergoes phosphorylation during mitosis, but not on its canonical TEY activation motif.
  • Five novel mitotic phosphorylation sites were identified, with two previously unknown.
  • Mitotic ERK5 phosphorylation is dependent on cyclin-dependent kinases (CDKs), not MEK5.
  • Phosphorylation of identified residues inhibits ERK5 activity and regulates its cytoplasmic-to-nuclear shuttling.

Conclusions:

  • Mitosis involves a novel, CDK-dependent phosphorylation-based regulation of ERK5 activity and localization.
  • This regulatory mechanism impacts ERK5 function independently of its activation motif.
  • The findings establish a link between CDK and ERK5 pathways, crucial for accurate cell cycle progression.

More Related Videos

Identification of Cyclin-dependent Kinase 1 Specific Phosphorylation Sites by an In Vitro Kinase Assay12:26

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

Published on: May 3, 2018

Monitoring Kinase and Phosphatase Activities Through the Cell Cycle by Ratiometric FRET13:38

Monitoring Kinase and Phosphatase Activities Through the Cell Cycle by Ratiometric FRET

Published on: January 27, 2012

Related Concept Videos

Positive Regulator Molecules02:39

Positive Regulator Molecules

Mitotic cell division results in daughter cells that exactly resemble the parent cell. However, errors in the DNA replication or distribution of genetic material may lead to genetic mutations that may be passed down to every new cell formed from the resulting abnormal cell. Propagation of such mutant cells is restricted through checkpoint mechanisms present at different stages of the cell cycle. These checkpoints involve regulator molecules that either promote or demote cell cycle events.
Positive Regulator Molecules01:45

Positive Regulator Molecules

To consistently produce healthy cells, the cell cycle—the process that generates daughter cells—must be precisely regulated.
Inhibition of Cdk Activity02:34

Inhibition of Cdk Activity

The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
Inhibition of CDK Activity02:34

Inhibition of CDK Activity

The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
The Cell Cycle Control System01:28

The Cell Cycle Control System

The cell cycle regulation directs how a cell proceeds from one phase to the next and begins mitosis. The cell cycle control system includes intracellular regulatory molecules and external triggers. They provide "stop" or "advance" signals and operate at specific cell cycle stages termed checkpoints to ensure that a particular process is completed before the cell advances to the next phase.
Cyclins and cyclin-dependent kinases (Cdks) are the primary cell cycle regulators and function at the cell...
The Cell Cycle Control System02:11

The Cell Cycle Control System

The cell cycle is an organized set of events that leads the cell to divide into two daughter cells, each containing chromosomes identical to the parent cell. It is the cell cycle that leads to the formation of an entire organism from a single-cell zygote. Besides, cell division also functions in the renewal or repair of tissues in adult multicellular eukaryotes. For example, in the bone marrow, the stem cells divide to form new blood cells. Although essential for several functions, cell...