Related Experiment Video
Updated: Jun 23, 2026
08:05
Assaying Protein Kinase Activity with Radiolabeled ATP
Published on: May 26, 2017
Erk1/2 MAP kinases are required for epidermal G2/M progression
Phillip A Dumesic1, Florence A Scholl, Deborah I Barragan
1Veterans Affairs Palo Alto Health Care System, Palo Alto, CA 94304, USA.
The Journal of Cell Biology
|May 6, 2009
Summary
Extracellular signal-regulated kinase (Erk)1/2 are crucial for normal epithelial tissue renewal. Simultaneous depletion of Erk1/2 inhibits cell division, leading to G2/M arrest, highlighting their essential role in epithelial self-renewal.
Area of Science:
- Cell Biology
- Molecular Biology
- Cancer Research
Background:
- Mitogen-activated protein kinases (MAPKs), specifically Erk1/2, are frequently hyperactivated in human cancers.
- The role of Erk1/2 in normal epithelial tissue, where most Erk-associated cancers originate, remains largely unknown.
- Previous studies focused on Erk1/2 function in fibroblasts, revealing distinct cell cycle regulation compared to epithelial cells.
Purpose of the Study:
- To investigate the function of Erk1/2 in normal epithelial tissue self-renewal.
- To determine the specific cell cycle phase regulated by Erk1/2 in epithelial cells.
- To elucidate the molecular mechanisms underlying Erk1/2-dependent cell cycle progression in epidermis.
Main Methods:
- Simultaneous depletion of Erk1 and Erk2 in mouse epidermis using genetic approaches.
- Analysis of cell division, proliferation, and cell cycle progression following Erk1/2 loss.
- Rescue experiments involving reintroduction of Erk2 or activation of downstream effectors.
- Gene expression analysis, focusing on cell cycle regulators like cyclin B1 and c-Fos.
Main Results:
- Individual loss of Erk1 or Erk2 had no discernible effect on epidermal tissue.
- Simultaneous depletion of Erk1/2 significantly inhibited cell division and tissue self-renewal.
- Growth inhibition was rescued by Erk2 reintroduction but not by activating G1 progression effectors.
- Erk1/2 loss in epithelial cells led to reduced cyclin B1 and c-Fos expression, causing G2/M arrest.
- A disruption of the cyclin B1-Cdc2 gene regulatory network was observed.
Conclusions:
- Erk1/2 are essential for the self-renewal of normal epithelial tissues.
- Unlike fibroblasts, Erk1/2 in epithelial cells are required for progression through the G2/M phase of the cell cycle.
- Erk1/2 signaling plays a critical role in maintaining epithelial tissue homeostasis by regulating the G2/M transition.
More Related Videos
Related Concept Videos
01:07MAPK 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...
02:15M-Cdk Drives Transition Into Mitosis
Checkpoints throughout the cell cycle serve as safeguards and gatekeepers, allowing the cell cycle to progress in favorable conditions and slow or halt it in problematic ones. This regulation is known as the cell cycle control system.
Cyclin-dependent kinases, or Cdks, work in concert with cyclins to control cell cycle transitions. M-Cdk, a complex of Cdk1 bound to M cyclin, is a well-known example of this coordinated control that drives the transition from the G2 to the M phase.
M cyclin...
Cyclin-dependent kinases, or Cdks, work in concert with cyclins to control cell cycle transitions. M-Cdk, a complex of Cdk1 bound to M cyclin, is a well-known example of this coordinated control that drives the transition from the G2 to the M phase.
M cyclin...
02:15M-Cdk Drives Transition Into Mitosis
Checkpoints throughout the cell cycle serve as safeguards and gatekeepers, allowing the cell cycle to progress in favorable conditions and slow or halt it in problematic ones. This regulation is known as the cell cycle control system.
Cyclin-dependent kinases, or Cdks, work in concert with cyclins to control cell cycle transitions. M-Cdk, a complex of Cdk1 bound to M cyclin, is a well-known example of this coordinated control that drives the transition from the G2 to the M phase.
M cyclin...
Cyclin-dependent kinases, or Cdks, work in concert with cyclins to control cell cycle transitions. M-Cdk, a complex of Cdk1 bound to M cyclin, is a well-known example of this coordinated control that drives the transition from the G2 to the M phase.
M cyclin...
02:38Mitogens and the Cell Cycle
Mitogens and their receptors play a crucial role in controlling the progression of the cell cycle. However, the loss of mitogenic control over cell division leads to tumor formation. Therefore, mitogens and mitogen receptors play an important role in cancer research. For instance, the epidermal growth factor (EGF) - a type of mitogen and its transmembrane receptor (EGFR), decides the fate of the cell's proliferation. When EGF binds to EGFR, a member of the ErbB family of tyrosine kinase...
02:34Inhibition 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...
02:39Positive 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.