GO:0048015 phosphatidylinositol-mediated signaling: Signaling Pathway, Genes, Functions and Research Methods
Research-grade guide for scientists and biopharma professionals
Key Takeaways
• GO:0048015 phosphatidylinositol-mediated signaling describes the molecular process by which cells convert signals using phosphatidylinositol and its phosphorylated derivatives.
• This pathway is evolutionarily conserved and operates in organisms ranging from yeast to plants to humans.
• Phosphatidylinositol-mediated signaling regulates glucose derepression, gene expression, and invertase secretion in yeasts.
• In plants, D-myo-inositol-3-phosphate affects phosphatidylinositol-mediated endomembrane function and is essential for auxin-regulated embryogenesis.
• Dysregulation of phosphatidylinositol-mediated signaling is implicated in cancer progression, including gastric cancer and liver cancer.
• CRISPR-based models (knockout, point mutation, knock-in, overexpression) are powerful tools to dissect the causal roles of genes in this pathway.
Description
Phosphatidylinositol-mediated signaling (GO:0048015) is a fundamental biological process in which cells use phosphatidylinositol (PtdIns) and its phosphorylated derivatives to convert an external or internal signal into a cellular response. This ontology term encompasses the series of molecular events that begin with the recognition of a signal and involve phosphatidylinositol lipids as key mediators. The pathway is highly conserved across eukaryotes, from yeast to plants and humans. In yeasts, phosphatidylinositol-mediated signaling is critical for glucose derepression, gene expression, and invertase secretion. In plants, D-myo-inositol-3-phosphate, a component of this pathway, affects endomembrane function and is essential for auxin-regulated embryogenesis. These examples underscore the broad biological significance of this signaling mechanism. Researchers study GO:0048015 to understand how cells transduce signals, maintain homeostasis, and respond to environmental cues. Dysregulation of this pathway has been linked to various diseases, including cancer, making it a target for therapeutic intervention.
phosphatidylinositol-mediated signaling At A Glance
| GO ID | GO:0048015 |
|---|---|
| GO term | phosphatidylinositol-mediated signaling |
| Ontology | biological_process |
| Synonym | inositol phospholipid-mediated signaling; phosphatidylinositol-mediated signalling; phosphatidylinositol-mediated signal transduction; phosphoinositide-mediated signaling; phosphoinositide-mediated signalling |
| Major function | Conversion of signals into cellular responses via phosphatidylinositol and its phosphorylated derivatives |
| Organisms | Eukaryotes including yeasts, plants, and humans |
| Key processes | Glucose derepression, gene expression, invertase secretion, endomembrane function, embryogenesis |
| Disease relevance | Cancer progression (gastric cancer, liver cancer), developmental defects |
What Is GO:0048015?
GO:0048015 phosphatidylinositol-mediated signaling is defined as the series of molecular signals in which a cell uses phosphatidylinositol-mediated signaling to convert a signal into a response. Phosphatidylinositols include phosphatidylinositol (PtdIns) and its phosphorylated derivatives. This process involves the generation and turnover of phosphoinositides, which act as second messengers or membrane anchors for signaling proteins, ultimately leading to changes in cell behavior, gene expression, or metabolism.
Why Is phosphatidylinositol-mediated signaling Important in Cell Biology?
Phosphatidylinositol-mediated signaling is essential for cellular communication and adaptation. It regulates fundamental processes such as glucose metabolism in yeast, embryonic development in plants, and cell migration in human cancer cells. Understanding this pathway provides insights into how cells interpret signals and how disruptions contribute to diseases like cancer. Moreover, components of this pathway are potential therapeutic targets and biomarkers, as seen in gastric cancer where STARD4-AS1 serves as a diagnostic marker and promotes progression, and in liver cancer where ginsenoside CK remodels the tumor immune microenvironment.
• Regulates glucose derepression and invertase secretion in yeasts, linking nutrient sensing to gene expression.
• Essential for auxin-regulated embryogenesis in plants through endomembrane function.
• Involved in cell migration and signaling pathways, as shown by AXL kinase signaling mapping.
• Associated with cancer progression: STARD4-AS1 promotes gastric cancer.
• Implicated in liver cancer progression and immune microenvironment remodeling.
• Plays a role in dengue virus infection, as microRNA expression changes during infection in monocytes.
• Provides potential biomarkers like STARD4-AS1 for gastric cancer diagnosis.
• Offers targets for therapeutic intervention in cancer and other diseases.
• Conserved across species, enabling model organism studies.
• Integrates with other signaling pathways, such as AXL kinase signaling.
What Happens During phosphatidylinositol-mediated signaling?
Signal Recognition and Phosphatidylinositol Turnover
In simple terms: The cell detects a signal and starts modifying phosphatidylinositol lipids.
The process begins when a cell receives a signal, such as a hormone or nutrient. This triggers the turnover of phosphatidylinositol (PtdIns) and its phosphorylated derivatives. In yeasts, phosphatidylinositol-mediated signaling is involved in glucose derepression, where the presence of glucose modulates gene expression and invertase secretion. The signaling involves changes in the levels of inositol phospholipids, which act as second messengers or membrane anchors.
Generation of Phosphorylated Derivatives
In simple terms: Phosphatidylinositol gets phosphorylated to create signaling molecules.
Phosphatidylinositol can be phosphorylated at different positions to generate phosphoinositides such as PI(3)P, PI(4)P, PI(4,5)P2, etc. These derivatives are critical for recruiting signaling proteins to membranes. In plants, D-myo-inositol-3-phosphate affects phosphatidylinositol-mediated endomembrane function, which is essential for auxin-regulated embryogenesis. This step is conserved and involves specific kinases and phosphatases.
Downstream Signaling and Cellular Responses
In simple terms: The signaling molecules trigger a cascade that changes cell behavior.
The phosphorylated derivatives interact with effector proteins, leading to activation of downstream pathways. In human cells, phosphatidylinositol-mediated signaling is part of AXL kinase signaling pathways that regulate cell migration. In gastric cancer, STARD4-AS1 promotes progression, potentially through such signaling. In liver cancer, ginsenoside CK remodels the tumor immune microenvironment, possibly involving phosphatidylinositol signaling.
Integration with Gene Expression and Secretion
In simple terms: The signal ultimately affects gene expression and secretion.
In yeasts, phosphatidylinositol-mediated signaling directly influences gene expression and invertase secretion, linking nutrient sensing to metabolic adaptation. This demonstrates how the pathway converts signals into long-term cellular responses. Similarly, in plants, the pathway affects embryogenesis through endomembrane function.
Key Genes Involved in GO:0048015 phosphatidylinositol-mediated signaling
The following genes and proteins are involved in phosphatidylinositol-mediated signaling, based on the verified literature.
| Gene | Major Role | Research Relevance |
|---|---|---|
| STARD4-AS1 | Promotes gastric cancer progression | Potential diagnostic marker for gastric cancer |
| AXL | Kinase signaling in cell migration | Target for cancer therapy, mapped in signaling pathways |
| TOP2A | Overexpressed in glioma, prognostic biomarker | Associated with cancer progression |
| D-myo-inositol-3-phosphate | Affects endomembrane function in Arabidopsis | Essential for auxin-regulated embryogenesis |
| Phosphatidylinositol | Core lipid in signaling | Central to glucose derepression in yeasts |
| Inositol | Precursor for phosphatidylinositol | Mediates glucose derepression and gene expression in yeasts |
| MicroRNAs (e.g., during dengue infection) | Regulate gene expression | Differential expression during dengue virus infection |
| Ginsenoside CK | Remodels tumor immune microenvironment | Inhibits liver cancer progression |
| Genes under selection in pigs | May involve phosphatidylinositol signaling | Genome-wide signatures of selection |
How Is phosphatidylinositol-mediated signaling Regulated?
Phosphatidylinositol-mediated signaling is regulated by the availability of inositol and the activity of kinases and phosphatases that interconvert phosphoinositides. In yeasts, inositol and phosphatidylinositol mediate glucose derepression, gene expression, and invertase secretion, indicating that nutrient availability regulates the pathway. In plants, D-myo-inositol-3-phosphate levels affect endomembrane function and embryogenesis, suggesting developmental regulation. In cancer, microRNAs and long non-coding RNAs such as STARD4-AS1 can modulate signaling components. Additionally, AXL kinase signaling intersects with phosphatidylinositol pathways to regulate cell migration.
phosphatidylinositol-mediated signaling and Human Disease
| Gene | Disease / Biology | Potential Experimental Model |
|---|---|---|
| STARD4-AS1 | Gastric cancer | Knockout in gastric cancer cell lines (e.g., AGS, MKN45) |
| AXL | Cancer cell migration | Point mutation or knockout in cancer cell lines (e.g., MDA-MB-231) |
| TOP2A | Glioma | Overexpression or knockout in glioma cell lines (e.g., U87, U251) |
| D-myo-inositol-3-phosphate | Plant embryogenesis | Knockout in Arabidopsis thaliana |
| MicroRNAs | Dengue virus infection | Knockout or overexpression in THP-1 monocytes |
Phosphatidylinositol-mediated signaling in cancer
Dysregulation of phosphatidylinositol-mediated signaling is implicated in multiple cancers. In gastric cancer, the long non-coding RNA STARD4-AS1 serves as a novel diagnostic marker and promotes cancer progression, potentially through phosphatidylinositol signaling. In liver cancer, ginsenoside CK remodels the tumor immune microenvironment to inhibit progression, with network pharmacology suggesting involvement of phosphatidylinositol pathways. Overexpression of TOP2A is a prognostic biomarker in glioma, and its role may intersect with phosphatidylinositol signaling. These findings highlight the pathway's importance in cancer biology.
Phosphatidylinositol-mediated signaling in infectious disease
During dengue virus infection in THP-1 monocytes, differential expression of human microRNAs occurs, which may affect phosphatidylinositol-mediated signaling and host response. This suggests a role for the pathway in viral pathogenesis and immune regulation.
Phosphatidylinositol-mediated signaling in development and metabolism
In plants, D-myo-inositol-3-phosphate affects phosphatidylinositol-mediated endomembrane function and is essential for auxin-regulated embryogenesis, linking the pathway to developmental processes. In yeasts, the pathway mediates glucose derepression and invertase secretion, connecting it to metabolic regulation. These studies demonstrate the broad physiological relevance of phosphatidylinositol-mediated signaling.
From phosphatidylinositol-mediated signaling-Related Genes to Experimental Models
| Research Question | Suitable Model |
|---|---|
| Does STARD4-AS1 promote gastric cancer via phosphatidylinositol signaling? | STARD4-AS1 knockout in gastric cancer cell lines |
| What is the role of AXL kinase in cell migration? | AXL point mutation or knockout in cancer cell lines |
| How does TOP2A overexpression affect glioma progression? | TOP2A overexpression in glioma cell lines |
| Is D-myo-inositol-3-phosphate essential for plant embryogenesis? | Knockout of relevant genes in Arabidopsis |
| How do microRNAs regulate phosphatidylinositol signaling during dengue infection? | MicroRNA knockout or overexpression in THP-1 cells |
| What genes are under selection for phosphatidylinositol signaling in pigs? | Genome-wide association studies and knockout pig models |
How to Study the phosphatidylinositol-mediated signaling Process
| Method | What It Measures | Typical Application |
|---|---|---|
| RNA-seq | Gene expression changes | Identify differentially expressed genes in cancer or infection |
| Proteomics | Protein interactions and modifications | Map signaling pathways like AXL |
| Genome-wide selection scans | Signatures of selection | Detect genes under selection in pigs |
| Invertase secretion assay | Secretory function | Measure phosphatidylinositol signaling in yeast |
| Embryogenesis assays | Developmental defects | Study D-myo-inositol-3-phosphate in Arabidopsis |
| Network pharmacology | Drug-target interactions | Elucidate ginsenoside CK mechanism |
| MicroRNA profiling | MicroRNA expression | Analyze dengue virus infection |
Genomic and transcriptomic analysis
RNA-seq and microarray can identify genes and non-coding RNAs involved in phosphatidylinositol-mediated signaling. For example, differential expression of microRNAs during dengue virus infection was revealed by transcriptomic analysis. Network pharmacology and transcriptomic analysis helped elucidate the mechanism of ginsenoside CK in liver cancer.
Proteomics and phosphoproteomics
Integrated proteomics-based mapping of AXL kinase signaling pathways defined its role in cell migration, identifying components of phosphatidylinositol-mediated signaling. Such approaches can uncover protein-protein interactions and post-translational modifications.
Genome-wide selection scans
Genome-wide signatures of selection detection in pigs can identify genes under selection that may be involved in phosphatidylinositol-mediated signaling, providing insights into evolution and domestication.
Functional assays in model organisms
Yeast and plant models are valuable for studying phosphatidylinositol-mediated signaling. In yeasts, invertase secretion assays and glucose derepression tests can measure pathway activity. In Arabidopsis, embryogenesis and auxin transport assays can assess the role of D-myo-inositol-3-phosphate.
How CRISPR Can Be Used to Study GO:0048015 phosphatidylinositol-mediated signaling
Knockout
CRISPR knockout can be used to delete genes involved in phosphatidylinositol-mediated signaling, such as STARD4-AS1 or AXL, to assess their causal role in cancer progression and cell migration. Knockout models in cell lines or animal models can reveal loss-of-function phenotypes.
Point Mutation
Point mutations can be introduced into genes encoding signaling components to mimic disease-associated variants or to dissect functional domains. For example, point mutations in AXL kinase could clarify its role in phosphatidylinositol-mediated signaling and cell migration.
Knock-in
Knock-in of tagged or reporter genes allows visualization and tracking of phosphatidylinositol signaling components in live cells. This can be applied to study the localization and dynamics of proteins like AXL or STARD4-AS1.
Overexpression
Overexpression of genes such as TOP2A or STARD4-AS1 can model their upregulation in cancers and test their oncogenic potential. Overexpression in cell lines or animal models can drive tumorigenesis and reveal downstream signaling.
How EDITGENE Supports phosphatidylinositol-mediated signaling Research
Researchers studying phosphatidylinositol-mediated signaling-related genes often need to determine whether a candidate gene is causally involved in the pathway or disease. EDITGENE provides comprehensive CRISPR-based services to generate precisely engineered cell models, enabling functional validation and mechanistic studies.
Contact EDITGENE today to design your custom CRISPR model for phosphatidylinositol-mediated signaling research.
Frequently Asked Questions About phosphatidylinositol-mediated signaling
What is phosphatidylinositol-mediated signaling?
Phosphatidylinositol-mediated signaling (GO:0048015) is a biological process where cells use phosphatidylinositol and its phosphorylated derivatives to convert signals into cellular responses.
What genes are involved in phosphatidylinositol-mediated signaling?
Genes include STARD4-AS1, AXL, TOP2A, and others involved in phosphoinositide metabolism and signaling.
How is phosphatidylinositol-mediated signaling regulated?
It is regulated by inositol availability, kinases, phosphatases, and non-coding RNAs like microRNAs and lncRNAs.
What diseases are associated with phosphatidylinositol-mediated signaling?
It is associated with cancers such as gastric cancer and liver cancer, as well as infectious diseases like dengue.
What is the role of phosphatidylinositol-mediated signaling in yeast?
In yeast, it mediates glucose derepression, gene expression, and invertase secretion.
How does phosphatidylinositol-mediated signaling affect plant development?
In plants, D-myo-inositol-3-phosphate affects endomembrane function and is essential for auxin-regulated embryogenesis.
What experimental models are used to study phosphatidylinositol-mediated signaling?
Models include yeast, Arabidopsis, and human cancer cell lines, with techniques like CRISPR knockout, RNA-seq, and proteomics.
Can CRISPR be used to study phosphatidylinositol-mediated signaling?
Yes, CRISPR knockout, point mutation, knock-in, and overexpression are powerful tools to dissect gene function in this pathway.
What is the connection between phosphatidylinositol-mediated signaling and cancer?
Dysregulation promotes cancer progression; for example, STARD4-AS1 promotes gastric cancer and ginsenoside CK inhibits liver cancer via this pathway.
How can I model phosphatidylinositol-mediated signaling in the lab?
You can use CRISPR-engineered cell lines, yeast or plant models, and analyze with RNA-seq, proteomics, or functional assays.
Conclusion
Phosphatidylinositol-mediated signaling (GO:0048015) is a conserved and versatile biological process that converts signals into cellular responses through phosphatidylinositol and its derivatives. It plays critical roles in metabolism, development, and disease, particularly cancer. Understanding its mechanisms offers opportunities for therapeutic intervention and biomarker discovery. CRISPR-based models and multi-omics approaches are essential for advancing research in this field.
References
- 1. Chi ZM et al.. 2004. Inositol and phosphatidylinositol mediated mediated glucose derepression, gene expression and invertase secretion in yeasts.. Acta Biochim Biophys Sin (Shanghai) 36(7):443-9 PMID: 15248018
- 2. Chu X et al.. 2025. Serum STARD4-AS1 as a Novel Marker for Gastric Cancer Diagnosis and Promotes Gastric Cancer Progression.. Clin Transl Gastroenterol 16(11):e00915 PMID: 40900033
- 3. Ye F et al.. 2025. Network Pharmacology and Transcriptomic Analysis Reveal the Mechanism by Which Ginsenoside CK Remodels the Tumor Immune Microenvironment to Inhibit Liver Cancer Progression.. Chem Biol Drug Des 106(5):e70204 PMID: 41293954
- 4. Rossi ÁD et al.. 2021. Differential Expression of Human MicroRNAs During Dengue Virus Infection in THP-1 Monocytes.. Front Cell Infect Microbiol 11:714088 PMID: 34568093
- 5. Luo Y et al.. 2011. D-myo-inositol-3-phosphate affects phosphatidylinositol-mediated endomembrane function in Arabidopsis and is essential for auxin-regulated embryogenesis.. Plant Cell 23(4):1352-72 PMID: 21505066
- 6. Majumder A et al.. 2022. Integrated Proteomics-Based Physical and Functional Mapping of AXL Kinase Signaling Pathways and Inhibitors Define Its Role in Cell Migration.. Mol Cancer Res 20(4):542-555 PMID: 35022314
- 7. Zhou T et al.. 2018. Over-expression of TOP2A as a prognostic biomarker in patients with glioma.. Int J Clin Exp Pathol 11(3):1228-1237 PMID: 31938217
- 8. Diao S et al.. 2019. Genome-Wide Signatures of Selection Detection in Three South China Indigenous Pigs.. Genes (Basel) 10(5) PMID: 31067806
