Related Experiment Video

Updated: Jun 1, 2026

A Guide to Production, Crystallization, and Structure Determination of Human IKK1/α
11:27

A Guide to Production, Crystallization, and Structure Determination of Human IKK1/α

Published on: November 2, 2018

A critical step for JNK activation: isomerization by the prolyl isomerase Pin1

J E Park1, J A Lee, S G Park

  • 1Medical Proteomics Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, Korea.

Cell Death and Differentiation
|June 11, 2011
PubMed

Insights

Pin1 isomerase is crucial for c-Jun N-terminal kinase (JNK) activation following stress. Pin1 binding and isomerization of phospho-Thr-Pro motifs in JNK1 enhance substrate association and cellular stress responses.

Area of Science:

  • Molecular Biology
  • Cellular Biology
  • Biochemistry

Background:

  • c-Jun N-terminal kinase (JNK) activation by stress involves dual phosphorylation but lacks detailed molecular mechanisms.
  • Understanding JNK activation pathways is critical for cellular stress response research.

Purpose of the Study:

  • To elucidate the role of peptidyl-prolyl isomerase Pin1 in JNK1 activation.
  • To investigate the molecular mechanism by which Pin1 modulates JNK1 activity.

Main Methods:

  • Overexpression and siRNA knockdown of Pin1 in human breast cancer cell lines.
  • Analysis of JNK1 activity and Pin1-JNK1 association.
  • Prolyl isomerization assay of the phospho-Thr-Pro motif in JNK1.

Main Results:

  • Pin1 overexpression correlated with increased JNK activity, while Pin1 knockdown decreased it.
  • Pin1 directly associates with JNK1 and catalyzes isomerization of the phospho-Thr-Pro motif.
  • Pin1 facilitates JNK1 substrate binding, and Pin1-deficient cells show impaired JNK activation and oxidative stress resistance.

Conclusions:

  • Pin1 plays a key role in JNK1 activation by catalyzing conformational changes after stress-induced phosphorylation.
  • Pin1-mediated JNK1 activation is essential for cellular responses to extracellular signals and oxidative stress.

More Related Videos

Light-mediated Reversible Modulation of the Mitogen-activated Protein Kinase Pathway during Cell Differentiation and Xenopus Embryonic Development09:32

Light-mediated Reversible Modulation of the Mitogen-activated Protein Kinase Pathway during Cell Differentiation and Xenopus Embryonic Development

Published on: June 15, 2017

Isolation of CA1 Nuclear Enriched Fractions from Hippocampal Slices to Study Activity-dependent Nuclear Import of Synapto-nuclear Messenger Proteins10:03

Isolation of CA1 Nuclear Enriched Fractions from Hippocampal Slices to Study Activity-dependent Nuclear Import of Synapto-nuclear Messenger Proteins

Published on: August 10, 2014

Related Concept Videos

The JAK-STAT Signaling Pathway01:20

The JAK-STAT Signaling Pathway

Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as  SH2...
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...
PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

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 rapamycin-insensitive companion...
cAMP-dependent Protein Kinase Pathways01:25

cAMP-dependent Protein Kinase Pathways

Cyclic Adenosine Monophosphate (cAMP) is an essential second messenger that activates protein kinase A (PKA) and regulates various biological processes. A single epinephrine molecule binds to GPCR and activates several heterotrimeric G proteins, each stimulating multiple adenylyl cyclase, amplifying the signal, and synthesizing large numbers of cAMP molecules. Small changes in cAMP concentration affect PKA activity. The binding of four cAMP molecules induces a conformational change in PKA,...
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...