Related Experiment Video

Updated: Sep 2, 2026

Characterize Disease-related Mutants of RAF Family Kinases by Using a Set of Practical and Feasible Methods
07:49

Characterize Disease-related Mutants of RAF Family Kinases by Using a Set of Practical and Feasible Methods

Published on: July 17, 2019

Apparent "activation" of protein kinases by okadaic acid class tumor promoters

T Sassa1, W W Richter, N Uda

  • 1Cancer Prevention Division, National Cancer Center Research Institute, Tokyo, Japan.

Biochemical and Biophysical Research Communications
|March 31, 1989
PubMed

Insights

Okadaic acid activates specific protein kinases in mouse brain cytosol, distinct from protein kinase C. This finding suggests a novel mechanism for tumor promotion involving these newly identified kinases.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Cancer Research

Background:

  • Protein kinases and phosphatases play crucial roles in cellular signaling pathways.
  • Tumor promoters are agents that can enhance the effects of carcinogens, leading to cancer development.
  • Okadaic acid is a known tumor promoter that targets protein phosphatases.

Purpose of the Study:

  • To investigate the effect of okadaic acid and related compounds on protein kinase activity in mouse brain cytosol.
  • To identify novel protein kinases and signaling pathways involved in tumor promotion.

Main Methods:

  • Cytosolic fraction of mouse brain was prepared.
  • DEAE-cellulose column chromatography was used to separate protein kinase activities.
  • Enzyme assays were performed to measure protein kinase and phosphatase activities.
  • The effects of various tumor promoters, including okadaic acid, were assessed.

Main Results:

  • Two peaks of protein kinase activity were identified in mouse brain cytosol.
  • The first peak corresponded to protein kinase C.
  • The second peak contained protein kinases activated by okadaic acid and dinophysistoxin-1, but not by other tumor promoters.
  • This second peak also contained phosphatases, whose activity was inhibited by okadaic acid and dinophysistoxin-1.

Conclusions:

  • Okadaic acid activates specific protein kinases in mouse brain cytosol through a mechanism distinct from protein kinase C.
  • The findings suggest a novel pathway for tumor promotion involving okadaic acid-activated protein kinases and phosphatases.
  • This research provides new insights into the molecular mechanisms of chemical carcinogenesis.

More Related Videos

Deciphering the Structural Effects of Activating EGFR Somatic Mutations with Molecular Dynamics Simulation15:05

Deciphering the Structural Effects of Activating EGFR Somatic Mutations with Molecular Dynamics Simulation

Published on: May 20, 2020

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

mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or 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...
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...