Related Experiment Video

Updated: Jun 21, 2026

Preparation of Cell-lines for Conditional Knockdown of Gene Expression and Measurement of the Knockdown Effects on E4orf4-Induced Cell Death
13:54

Preparation of Cell-lines for Conditional Knockdown of Gene Expression and Measurement of the Knockdown Effects on E4orf4-Induced Cell Death

Published on: October 21, 2012

Par-4 is an essential downstream target of DAP-like kinase (Dlk) in Dlk/Par-4-mediated apoptosis

Meike Boosen1, Susanne Vetterkind, Jan Kubicek

  • 1Institute of Genetics, University of Bonn, D-53117 Bonn, Germany.

Molecular Biology of the Cell
|July 24, 2009
PubMed

Insights

Prostate apoptosis response-4 (Par-4) and DAP-like kinase (Dlk) induce apoptosis. Dlk phosphorylation of Par-4 at threonine 155 is essential for this cell death process.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • Prostate apoptosis response-4 (Par-4) is upregulated during apoptosis.
  • DAP-like kinase (Dlk/ZIPK) interacts with Par-4.

Purpose of the Study:

  • To investigate the mechanism of Dlk/Par-4-induced apoptosis.
  • To identify the role of Par-4 phosphorylation in apoptosis.

Main Methods:

  • Coexpression of Dlk and Par-4 in REF52.2 cells.
  • In vitro kinase assays with Par-4 phosphorylation mutants.
  • Use of phospho-specific antibodies.

Main Results:

  • Dlk/Par-4 complex formation induces apoptosis via actin filament relocation and MLC phosphorylation.
  • Threonine 155 (T155) is the primary site of Par-4 phosphorylation by Dlk.
  • Phosphorylation of Par-4 at T155 is critical for Dlk-mediated apoptosis induction.

Conclusions:

  • Dlk-mediated phosphorylation of Par-4 at T155 is a key event in Dlk/Par-4-induced apoptosis.
  • This phosphorylation event is essential for Dlk recruitment to actin filaments and subsequent apoptosis.

More Related Videos

Fluorescence-based Monitoring of PAD4 Activity via a Pro-fluorescence Substrate Analog08:37

Fluorescence-based Monitoring of PAD4 Activity via a Pro-fluorescence Substrate Analog

Published on: November 5, 2014

Development of Inhibitors of Protein-protein Interactions through REPLACE: Application to the Design and Development Non-ATP Competitive CDK Inhibitors10:33

Development of Inhibitors of Protein-protein Interactions through REPLACE: Application to the Design and Development Non-ATP Competitive CDK Inhibitors

Published on: October 26, 2015

Related Concept Videos

Anaphase Promoting Complex00:50

Anaphase Promoting Complex

The stepwise destruction of specific proteins is necessary for the progression and completion of the cell cycle. Such proteins are ubiquitinated by ubiquitin ligases and then subsequently destroyed by the proteasome. The SCF (Skp1/Cullin/F-box) and the anaphase-promoting complex (APC) are two important ubiquitin ligases involved in cell cycle progression. While SCF is active throughout the cell cycle, APC gets activated during metaphase to anaphase transition. Cdc20 or Cdh1 binds to APC and...
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...
MAPK Signaling Cascades01:07

MAPK 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...
Amplifying Signals via Enzymatic Cascade01:22

Amplifying Signals via Enzymatic Cascade

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 the...
Interactions Between Signaling Pathways01:19

Interactions Between Signaling Pathways

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...