Related Experiment Video
Updated: Nov 14, 2025
08:54
An Immunofluorescent Method for Characterization of Barrett’s Esophagus Cells
Published on: July 20, 2014
14.2K
c-Src facilitates tumorigenesis by phosphorylating and activating G6PD.
Huanhuan Ma1, Fengqiong Zhang1, Lin Zhou1
1State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network, School of Life Sciences, Xiamen University, Xiamen, Fujian, China.
Oncogene
|March 9, 2021
Summary
The proto-oncogene c-Src phosphorylates Glucose-6-phosphate dehydrogenase (G6PD), enhancing its activity and promoting cancer cell growth. This discovery deepens our understanding of c-Src
Area of Science:
- Biochemistry
- Oncology
- Molecular Biology
Background:
- Glucose-6-phosphate dehydrogenase (G6PD) is a key enzyme in the pentose phosphate pathway (PPP).
- Excessive PPP activation is implicated in tumorigenesis.
- The role of c-Src in regulating G6PD activity in cancer is not fully understood.
Purpose of the Study:
- To investigate the interaction between tyrosine kinase c-Src and G6PD.
- To determine if c-Src phosphorylates G6PD and its functional consequences.
- To explore the role of c-Src-mediated G6PD activation in tumorigenesis.
Main Methods:
- Co-immunoprecipitation assays to detect protein interactions.
- In vitro kinase assays to assess G6PD phosphorylation by c-Src.
- Enzyme kinetics studies to evaluate G6PD activity.
- Analysis of clinical colorectal cancer samples.
Main Results:
- c-Src directly interacts with and phosphorylates G6PD at tyrosine 112.
- Phosphorylation by c-Src significantly enhances G6PD catalytic activity (decreased Km, increased Kcat).
- Activated G6PD increases PPP flux, boosting NADPH and ribose-5-phosphate production, supporting cancer cell biosynthesis and ROS detoxification.
- c-Src activation correlates with G6PD tyrosine phosphorylation and activity in colorectal cancer.
Conclusions:
- c-Src acts as a proto-oncogene by phosphorylating and activating G6PD.
- This c-Src-G6PD axis promotes tumorigenesis through enhanced PPP activity.
- Targeting the c-Src-G6PD interaction may offer a therapeutic strategy for cancer.
Related Concept Videos
02:38The Ras Gene
6.7K
The Ras-gene-encoded proteins are regulators of signaling pathways controlling cell proliferation, differentiation, or cell survival. The Ras-gene family in humans constitutes three primary members—the HRas, NRas, and KRas. These genes code for four functionally distinct yet closely related proteins—the HRas, NRas, KRas4A, and KRas4B. The involvement of mutant Ras genes in human cancer was first discovered in 1982 and is among the most common causes of human tumorigenesis.
Ras is a...
Ras is a...
6.7K
03:03mTOR Signaling and Cancer Progression
4.0K
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...
The mTOR pathway or the...
4.0K
01:33Cancer-Critical Genes I: Proto-oncogenes
9.7K
Genes usually encode proteins necessary for the proper functioning of a healthy cell. Mutations can often cause changes to the gene expression pattern, thereby altering the phenotype.
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
9.7K
02:34Inhibition of Cdk Activity
5.3K
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...
5.3K
01:25cAMP-dependent Protein Kinase Pathways
7.3K
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,...
7.3K
01:09GPCRs Regulate Adenylyl Cylase Activity
6.4K
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...
6.4K