Related Experiment Video

Updated: Aug 9, 2026

Isolation of CA1 Nuclear Enriched Fractions from Hippocampal Slices to Study Activity-dependent Nuclear Import of Synapto-nuclear Messenger Proteins
10:03

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

Activation of the Sap-1a transcription factor by the c-Jun N-terminal kinase (JNK) mitogen-activated protein kinase

R Janknecht1, T Hunter

  • 1Molecular Biology and Virology Laboratory, The Salk Institute, La Jolla, California 92037, USA.

The Journal of Biological Chemistry
|February 14, 1997
PubMed

Insights

Stress-activated JNK-1 phosphorylates Ternary Complex Factor Sap-1a, enhancing gene transcription. This phosphorylation impacts different promoters and is modulated by other MAPKs, highlighting Sap-1a's role in cellular stress responses.

Area of Science:

  • Molecular Biology
  • Cellular Signaling
  • Gene Regulation

Background:

  • Ternary Complex Factors (TCFs) regulate gene expression, including the c-fos promoter, in response to extracellular stimuli.
  • The ERK subclass of MAPKs targets TCF Sap-1a, mediating promoter activation.
  • Understanding TCF regulation by different MAPK subclasses is crucial for deciphering cellular responses.

Purpose of the Study:

  • To investigate the role of the JNK MAPK subclass in phosphorylating and regulating TCF Sap-1a.
  • To determine the impact of JNK-mediated phosphorylation on Sap-1a's transcriptional activity at specific promoter elements.
  • To compare the regulatory mechanisms of Sap-1a by ERK and JNK MAPKs.

Main Methods:

  • Phosphorylation site mapping of Sap-1a by JNK-1.
  • Site-directed mutagenesis of identified phosphorylation sites.
  • Reporter gene assays to measure transcriptional activity in RK13 cells.
  • Comparative analysis of Sap-1a and Elk-1 responses to ERK-1 and JNK-1 stimulation.
  • Investigation of p38 MAPK inhibition on JNK-1 activation of Sap-1a.

Main Results:

  • JNK-1 phosphorylates Sap-1a, stimulating both c-fos serum response element and E74-site-dependent transcription.
  • Specific JNK-1 phosphorylation sites on Sap-1a were identified, and their mutation altered transactivation.
  • The effect of phosphorylation sites varied depending on the promoter and the specific MAPK (ERK-1 or JNK-1) involved.
  • Sap-1a and Elk-1 exhibited differential responses to ERK-1 and JNK-1.
  • p38 MAPK inhibited JNK-1-mediated activation of Sap-1a in RK13 cells.

Conclusions:

  • Sap-1a is a key mediator of nuclear responses to cellular stress via JNK-mediated phosphorylation.
  • Differential regulation of Sap-1a by distinct MAPK pathways (JNK vs. ERK) provides pathway-specific transcriptional control.
  • Cross-talk between MAPK pathways, such as inhibition by p38 MAPK, influences Sap-1a activity.

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

Intracellular Phosphoflow Cytometry of Acute Myeloid Leukemia Patient-Derived Xenotransplants07:38

Intracellular Phosphoflow Cytometry of Acute Myeloid Leukemia Patient-Derived Xenotransplants

Published on: June 6, 2025

Related Concept Videos

Mitogens and the Cell Cycle02:38

Mitogens 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...
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...
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...
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...
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...
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,...