Related Experiment Video
Updated: Jan 30, 2026
08:00
Spatiotemporal Control of Protein Activity through Optogenetic Allosteric Regulation
Published on: October 4, 2024
1.1K
c-Src regulates Nrf2 activity through PKCδ after oxidant stimulus
Lígia Fão1, Sandra I Mota2, A Cristina Rego1
1Center for Neuroscience and Cell Biology (CNC), University of Coimbra, Coimbra, Portugal; Institute of Biochemistry, Faculty of Medicine, University of Coimbra, Coimbra, Portugal.
Biochimica Et Biophysica Acta. Molecular Cell Research
|January 28, 2019
Summary
Hydrogen peroxide (H2O2) activates the c-Src/PKCδ/Nrf2 pathway, enhancing cell defense enzyme expression. This pathway, regulated by c-Src kinase, offers a potential therapeutic target for redox-related disorders.
Area of Science:
- Cellular signaling pathways
- Redox biology
- Neuroscience
Background:
- Nuclear factor erythroid 2-related factor 2 (Nrf2) regulates cell defense enzymes and is implicated in oxidant-related disorders.
- Protein kinase C delta (PKCδ) and Src tyrosine kinases modulate Nrf2 activity.
- Src family kinases are involved in cellular processes and regulated by hydrogen peroxide (H2O2).
Purpose of the Study:
- To investigate the activation of c-Src and Nrf2 signaling proteins.
- To determine the influence of c-Src kinase on Nrf2 regulation following H2O2 exposure.
- To elucidate the role of the c-Src/PKCδ/Nrf2 pathway in cellular response to oxidative stress.
Main Methods:
- Exposure of HT22 mouse hippocampal neural cells to H2O2.
- Analysis of c-Src and Nrf2 phosphorylation and activation.
- Assessment of Nrf2 nuclear accumulation and transcriptional activity (HO-1 expression).
- Investigation of PKCδ phosphorylation at Tyr311.
Main Results:
- Acute H2O2 exposure increased phosphorylation/activation of c-Src (Tyr416) and Nrf2 (Ser40).
- c-Src kinase activation was essential for Nrf2 phosphorylation at Ser40, nuclear accumulation, and HO-1 expression.
- c-Src modulated Nrf2 activity via PKCδ phosphorylation at Tyr311.
Conclusions:
- The study demonstrates, for the first time, c-Src-mediated regulation of Nrf2 transcriptional activity through PKCδ activation following H2O2 stimulus.
- The c-Src/PKCδ/Nrf2 pathway represents a novel signaling cascade activated by H2O2.
- This pathway is a potential therapeutic target for diseases associated with redox deregulation.
Related Concept Videos
03:14Oxidation Numbers
42.5K
In redox reactions, the transfer of electrons occurs between reacting species. Electron transfer is described by a hypothetical number called the oxidation number (or oxidation state). It represents the effective charge of an atom or element, which is assigned using a set of rules.
42.5K
01:11Enteric Nervous System: Regulation of GI Motor Activity
1.8K
The Enteric Nervous System (ENS) plays a pivotal role in regulating gastrointestinal or GI motor activity. This complex network of nerves, deeply embedded within the gut wall, responds to changes in the gut environment and receives input from both the autonomic nervous system and the central nervous system. By doing so, the ENS operates various programs tailored to the body's nutritional status and needs.
During periods of fasting, the ENS initiates the migrating myoelectric complex, a...
During periods of fasting, the ENS initiates the migrating myoelectric complex, a...
1.8K
01:09GPCRs Regulate Adenylyl Cylase Activity
7.5K
Some GPCRs transmit signals through adenylyl cyclase (AC), a transmembrane enzyme. AC helps synthesize second messenger cyclic adenosine monophosphate (cAMP). AC catalyzes cyclization reaction and converts ATP to cAMP by releasing a pyrophosphate. The pyrophosphate is further hydrolyzed to phosphate by the enzyme pyrophosphatase, which drives cAMP synthesis to completion. However, cAMP is rapidly degraded to 5′ AMP by the enzymes phosphodiesterase (PDE), preventing overstimulation of...
7.5K
01:15Pyruvate Oxidation
168.8K
After glycolysis, the charged pyruvate molecules enter the mitochondria via active transport and undergo three enzymatic reactions. These reactions ensure that pyruvate can enter the next metabolic pathway so that energy stored in the pyruvate molecules can be harnessed by the cells.
First, the enzyme pyruvate dehydrogenase removes the carboxyl group from pyruvate and releases it as carbon dioxide. The stripped molecule is then oxidized and releases electrons, which are then picked up by NAD+...
First, the enzyme pyruvate dehydrogenase removes the carboxyl group from pyruvate and releases it as carbon dioxide. The stripped molecule is then oxidized and releases electrons, which are then picked up by NAD+...
168.8K
02:14GTPases and their Regulation
9.8K
Guanine nucleotide-binding proteins (G-proteins), also known as GTPases, are a superfamily of proteins that regulate many cellular processes, such as cell signaling, vesicular transport, and the regulation of cell shape and motility. Mutation or dysfunction of these proteins can lead to disease. There are around 40,000 known G-proteins that can broadly be classified into two groups ‒ small G-proteins consisting of a single domain and large multi-domain G-proteins.
Large G-proteins,...
Large G-proteins,...
9.8K
02:58Regulated Protein Degradation
8.8K
It is vital to regulate the activity of enzymatic as well as non-enzymatic proteins inside the cell. This can be achieved either through creating a balance between their rate of synthesis and degradation or regulating the intrinsic activity of the protein. Both these regulation mechanisms play an essential role in the normal functioning of cells.
Protein degradation plays two important roles in the cells. It helps to protect cells from misfolded or damaged proteins before they lead to a...
Protein degradation plays two important roles in the cells. It helps to protect cells from misfolded or damaged proteins before they lead to a...
8.8K