Related Experiment Video

Updated: Aug 13, 2026

Assaying Protein Kinase Activity with Radiolabeled ATP
08:05

Assaying Protein Kinase Activity with Radiolabeled ATP

Published on: May 26, 2017

Protein kinase G activates the JNK1 pathway via phosphorylation of MEKK1

J W Soh1, Y Mao, L Liu

  • 1Department of Medicine, Herbert Irving Comprehensive Cancer Center, College of Physicians & Surgeons, Columbia University, New York, New York 10032, USA.

The Journal of Biological Chemistry
|March 30, 2001
PubMed

Insights

Exisulind induces colon cancer cell death by activating protein kinase G (PKG) and c-Jun kinase (JNK1). PKG directly phosphorylates MEKK1, initiating a novel pathway that activates JNK1 and promotes apoptosis.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Cancer Research

Background:

  • Exisulind and related compounds induce apoptosis in colon cancer cells.
  • This apoptosis is mediated by the activation of protein kinase G (PKG) and c-Jun kinase (JNK1).

Purpose of the Study:

  • To further elucidate the mechanism by which PKG and JNK1 activation leads to apoptosis.
  • To investigate the role of MEKK1 in the PKG-mediated activation of JNK1.

Main Methods:

  • Utilized NIH3T3 cells expressing a constitutively active mutant of PKG.
  • Employed dominant-negative MEKK1 to inhibit JNK1 activation.
  • Performed in vitro phosphorylation assays using purified PKG and MEKK1.

Main Results:

  • Constitutively active PKG dose-dependently activated JNK1 and transactivated c-Jun.
  • PKG-induced JNK1 activation and c-Jun transactivation were blocked by dominant-negative MEKK1.
  • Purified PKG directly phosphorylated MEKK1, enhancing its activity.

Conclusions:

  • PKG activates JNK1 through a novel pathway involving direct phosphorylation and activation of MEKK1.
  • This PKG-MEKK1-SEK1-JNK1 pathway is crucial for exisulind-induced apoptosis in colon cancer cells.

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

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...
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,...