GO:0023052 signaling: Signal Transduction Pathways, Genes, Functions and Research Methods
Research-grade guide for scientists and biopharma professionals
Key Takeaways
• GO:0023052 (signaling) is the biological process by which information is transmitted within a biological system, beginning with an active signal and ending when a cellular response is triggered.
• Signaling is a broad ontology term that encompasses receptor activation, second messenger generation, kinase cascades, and transcriptional reprogramming.
• Dysregulated signaling underlies major human diseases including cancer, where cascades such as MAPK, PI3K/AKT, and TGF-beta drive melanomagenesis and tumor microenvironment remodeling.
• Plant signaling systems, including salicylic acid transport and systemic acquired resistance, provide conserved paradigms for long-distance information transfer.
• Membrane receptor trafficking and palmitoylation dynamically tune signaling output, making these processes key experimental targets.
• CRISPR knockout, point-mutation, knock-in, and overexpression models are essential for causally dissecting signaling components in disease and development.
Description
GO:0023052 (signaling) is a Gene Ontology biological_process term defined as the entirety of a process in which information is transmitted within a biological system, beginning with an active signal and ending when a cellular response has been triggered. This term sits at the highest level of signal transduction ontology, encompassing receptor-ligand interactions, second messenger systems, kinase and phosphatase cascades, and downstream transcriptional or metabolic responses. Signaling is fundamental to how cells sense and respond to their environment, coordinate development, and maintain tissue homeostasis. In plants, signaling pathways control shoot and flower meristem activity and systemic defense responses, while in animals, signaling cascades govern apoptosis, immune surveillance, and tumor progression. Because signaling is a process rather than a single molecule, its study requires integrated genetic, biochemical, and imaging approaches. The breadth of GO:0023052 makes it a powerful organizing concept for researchers seeking to map genotype to phenotype across disease and developmental contexts.
signaling At A Glance
| GO ID | GO:0023052 |
|---|---|
| GO term | signaling |
| Ontology | biological_process |
| Synonym | biological signaling, signaling process, signalling, signalling process, single organism signaling |
| Major function | Transmission of information within a biological system from an active signal to a triggered cellular response |
| Definition source | QuickGO definition: The entirety of a process in which information is transmitted within a biological system. This process begins with an active signal and ends when a cellular response has been triggered. |
| Scope | Includes receptor activation, second messenger generation, kinase cascades, and transcriptional responses |
| Related processes | Calcium signaling, TGF-beta signaling, pattern-recognition receptor signaling, systemic acquired resistance |
| Organism examples | Arabidopsis thaliana meristem signaling, mammalian apoptosis and cancer signaling |
What Is GO:0023052?
In our own words, GO:0023052 (signaling) describes the complete sequence of events by which a biological system receives, transmits, and responds to information. The process starts with an active signal, such as a ligand, a physical cue, or a metabolic intermediate, and concludes when a cellular response has been triggered. This definition intentionally covers all signaling modalities, including paracrine, autocrine, endocrine, and long-distance systemic signaling. It does not specify a particular receptor or pathway, making it a parent term for more specific signaling processes such as calcium signaling, TGF-beta signaling, and pattern-recognition receptor signaling.
Why Is signaling Important in Cell Biology?
Signaling is important because nearly every physiological decision a cell makes, from division and differentiation to death and immune defense, depends on the accurate transmission of information. When signaling is corrupted, the consequences include cancer, autoimmune disease, developmental defects, and failure of systemic immune responses. Understanding signaling at the molecular level therefore provides both mechanistic insight and therapeutic targets, as illustrated by TGF-beta pathway inhibitors in oncology and salicylic acid transport in plant immunity.
• Signaling controls cell fate decisions including proliferation, differentiation, and apoptosis.
• Dysregulated signaling cascades such as MAPK and PI3K/AKT are central drivers of melanomagenesis and other cancers.
• TGF-beta signaling shapes the tumor microenvironment and is a validated target for cancer therapy.
• Pattern-recognition receptor signaling and calcium signaling coordinate innate immune responses.
• Long-distance salicylic acid signaling mediates systemic acquired resistance in plants.
• Meristem signaling in Arabidopsis determines shoot and flower architecture.
• Palmitoylation and trafficking of membrane receptors modulate signaling amplitude and duration.
• Apoptotic cell clearance depends on signaling between dying cells and phagocytes.
• Signaling pathways are the most frequent source of druggable targets in precision medicine.
• CRISPR-based models enable causal testing of signaling hypotheses in vivo and in vitro.
What Happens During signaling?
Signal perception and receptor activation
In simple terms: A signal molecule arrives and switches on a receptor, like a key turning a lock.
Signaling begins when an active signal, such as a ligand, hormone, or damage-associated molecule, binds to or activates a receptor. In plant immunity, salicylic acid is transported and perceived to initiate long-distance immune signaling. In mammals, pattern-recognition receptors detect microbial or damage signals and couple to calcium signaling machinery. Receptor activation often involves conformational changes, dimerization, or post-translational modifications such as palmitoylation that influence membrane trafficking and signaling capacity.
Second messenger generation and amplification
In simple terms: The cell makes small messenger molecules that spread the signal quickly.
Activated receptors generate second messengers such as calcium ions, cyclic nucleotides, or lipid derivatives. The crosstalk between pattern-recognition receptor signaling and calcium signaling illustrates how ion fluxes amplify and shape immune responses. These second messengers recruit downstream effectors, including kinases and phosphatases, that propagate the signal through the cytoplasm.
Kinase cascades and signal transduction
In simple terms: A chain of proteins passes the message along by adding phosphate tags.
Signal transduction frequently proceeds through sequential phosphorylation events in kinase cascades. Major signaling cascades in melanomagenesis, including MAPK and PI3K/AKT, depend on such phosphorylation relays to transmit signals from the membrane to the nucleus. TGF-beta signaling similarly uses receptor serine/threonine kinases and SMAD proteins to carry information into the nucleus.
Transcriptional and metabolic responses
In simple terms: The message reaches the nucleus or metabolic machinery and changes what the cell does.
The endpoint of signaling is a cellular response, which may include changes in gene expression, metabolism, or cytoskeletal organization. In shoot and flower meristems, signaling inputs converge on transcription factors that pattern developmental gene expression. In cancer, TGF-beta signaling reprograms the tumor microenvironment and immune cell behavior.
Signal termination and feedback
In simple terms: The cell switches the signal off so it does not stay on too long.
Signaling must be terminated or attenuated to prevent pathological overactivation. Receptor trafficking and palmitoylation status influence whether membrane receptors are recycled or degraded, thereby tuning signaling duration. Apoptotic cell clearance also requires timely termination signals to avoid inflammation.
Long-distance and systemic signaling
In simple terms: Signals can travel from one part of an organism to another.
Signaling is not limited to single cells. In plants, salicylic acid transport and systemic signaling coordinate defense across distant tissues. In animals, endocrine and cytokine signals similarly act at organism scale to integrate physiology.
Key Genes Involved in GO:0023052 signaling
The following genes and proteins represent core components and regulators of signaling processes across model organisms and human disease contexts.
| Gene | Major Role | Research Relevance |
|---|---|---|
| TGFB1 | Ligand for TGF-beta signaling | Tumor microenvironment and cancer therapy target |
| TGFBR1 | Type I TGF-beta receptor kinase | Point-mutation and knockout studies of signaling output |
| SMAD2 | Receptor-regulated SMAD transcription factor | Knockout models for TGF-beta transcriptional responses |
| SMAD3 | Receptor-regulated SMAD transcription factor | Knock-in reporters for signaling dynamics |
| MAPK1 | Extracellular signal-regulated kinase | Melanoma signaling cascade studies |
| BRAF | Serine/threonine kinase in MAPK pathway | Point-mutation models in melanoma |
| PIK3CA | Catalytic subunit of PI3K | Overexpression and knock-in cancer models |
| AKT1 | Serine/threonine kinase effector | Signaling cascade dissection |
| PRR receptors | Pattern-recognition receptors | Calcium signaling crosstalk studies |
| CALM1 | Calcium-binding messenger protein | Calcium signaling research |
| NLRP3 | Inflammasome sensor | Signaling in innate immunity |
| BAX | Pro-apoptotic effector | Apoptosis signaling models |
| CASP3 | Executioner caspase | Apoptotic signaling readouts |
| PALM proteins | Palmitoylation machinery | Membrane receptor trafficking studies |
| NPR1 | Plant salicylic acid signaling regulator | Systemic acquired resistance models |
| ICS1 | Salicylic acid biosynthesis enzyme | Plant immune signaling knockout studies |
| CLV3 | Meristem signaling peptide | Shoot meristem signaling research |
How Is signaling Regulated?
Signaling is regulated at multiple levels, including ligand availability, receptor abundance and trafficking, post-translational modifications, and feedback phosphorylation. Palmitoylation affects the trafficking and signaling of membrane receptors, thereby controlling signal duration and intensity. In plant immunity, salicylic acid transport and systemic signaling are tightly regulated to balance defense and growth. In cancer, TGF-beta signaling is modulated by the tumor microenvironment and can switch from tumor-suppressive to tumor-promoting depending on context. Calcium signaling crosstalk with pattern-recognition receptors provides another layer of regulation in innate immunity.
signaling and Human Disease
| Gene | Disease / Biology | Potential Experimental Model |
|---|---|---|
| BRAF | Melanoma | Point-mutation knock-in (V600E) in cell lines |
| TGFBR1 | Cancer and fibrosis | Knockout and point-mutation models |
| CASP3 | Apoptosis-related disorders | Knockout and overexpression models |
| NPR1 | Plant immunity | Knockout Arabidopsis lines |
| CLV3 | Meristem development | Knock-in reporter lines |
Cancer and dysregulated signaling cascades
Many cancers arise from mutations that constitutively activate signaling pathways. In melanoma, major signaling cascades including MAPK and PI3K/AKT are frequently altered, providing a rationale for targeted therapy. TGF-beta signaling in the tumor microenvironment promotes immune evasion and tumor progression, making it a therapeutic target.
Immune and inflammatory disorders
Pattern-recognition receptor signaling and calcium signaling are central to innate immune activation, and their dysregulation contributes to inflammatory disease. Apoptotic cell clearance signaling defects can lead to autoimmunity and chronic inflammation.
Plant disease and crop immunity
Salicylic acid transport and systemic acquired resistance are critical for plant defense against pathogens, and manipulating these signaling pathways is a strategy for crop protection.
Developmental disorders
Signaling in shoot and flower meristems controls plant architecture, and disruptions in meristem signaling lead to developmental abnormalities. In animals, analogous signaling defects underlie congenital malformations.
From signaling-Related Genes to Experimental Models
| Research Question | Suitable Model |
|---|---|
| Is a signaling gene required for pathway activation? | CRISPR knockout cell line |
| Does a specific mutation alter signaling output? | Point-mutation knock-in |
| Can a signaling reporter track pathway activity? | Tagged knock-in |
| Does overexpression drive oncogenic signaling? | Overexpression cell model |
| Which genes regulate a signaling cascade? | CRISPR library screening |
| How does a signaling protein localize dynamically? | Fluorescent knock-in |
How to Study the signaling Process
| Method | What It Measures | Typical Application |
|---|---|---|
| RNA-seq | Transcriptional changes | Pathway target identification |
| Phosphoproteomics | Phosphorylation sites | Kinase cascade mapping |
| Live-cell calcium imaging | Second messenger dynamics | PRR-calcium crosstalk |
| CRISPR knockout screen | Gene requirement | Signaling regulator discovery |
| CRISPR activation screen | Gene sufficiency | Pathway enhancer identification |
| Western blot | Protein abundance and modification | Receptor trafficking and palmitoylation |
| Flow cytometry | Cell population responses | Apoptosis signaling readouts |
Transcriptomic profiling of signaling responses
RNA-seq measures global transcriptional changes downstream of signaling activation, revealing pathway targets and feedback loops.
Phosphoproteomics and kinase activity assays
Phosphoproteomics quantifies phosphorylation events in kinase cascades, providing a direct readout of signaling flux.
Live-cell imaging of signaling dynamics
Fluorescent reporters and biosensors allow real-time visualization of second messengers such as calcium and of receptor trafficking.
Genetic screens and CRISPR libraries
CRISPR knockout and activation screens identify positive and negative regulators of signaling pathways in an unbiased manner.
How CRISPR Can Be Used to Study GO:0023052 signaling
Knockout
CRISPR knockout of signaling genes is used to test whether a candidate receptor, kinase, or transcription factor is required for a given response. For example, knocking out TGFBR1 or SMAD2 can abolish TGF-beta transcriptional output. In plant immunity, knocking out NPR1 or ICS1 disrupts salicylic acid signaling.
Point Mutation
Point-mutation knock-in models introduce specific amino acid changes to mimic disease alleles or to dissect catalytic residues. BRAF V600E knock-in is a classic example in melanoma signaling research. Such models are essential for distinguishing gain-of-function from loss-of-function mechanisms.
Knock-in
Tagged knock-in of signaling proteins with fluorescent or epitope tags enables real-time tracking of localization and interaction dynamics. CLV3 reporter knock-ins have been used to study meristem signaling in Arabidopsis. Similar approaches apply to mammalian receptor trafficking studies.
Overexpression
Overexpression models test whether increased abundance of a signaling component is sufficient to drive pathway activation or oncogenic transformation. Overexpression of PIK3CA or AKT1 can activate PI3K/AKT signaling in cancer models. In plants, overexpression of salicylic acid pathway genes can enhance defense.
How EDITGENE Supports signaling Research
Researchers studying signaling-related genes often need to determine whether a candidate gene is causally involved in a pathway, whether a specific mutation alters signaling output, or whether a signaling protein can be tracked in live cells. EDITGENE provides end-to-end CRISPR services to generate precisely engineered cell models that answer these questions.
Contact EDITGENE today to design your custom CRISPR model for signaling research.
Frequently Asked Questions About signaling
What is GO:0023052 signaling?
GO:0023052 is a Gene Ontology biological_process term defined as the entirety of a process in which information is transmitted within a biological system, beginning with an active signal and ending when a cellular response has been triggered.
What genes are involved in signaling?
Key signaling genes include TGFB1, TGFBR1, SMAD2/3, MAPK1, BRAF, PIK3CA, AKT1, CALM1, CASP3, and plant genes such as NPR1 and ICS1.
How is signaling regulated?
Signaling is regulated by ligand availability, receptor trafficking and palmitoylation, phosphorylation feedback, and second messenger dynamics.
What diseases are linked to defective signaling?
Cancer, inflammatory disorders, autoimmune diseases, and plant immune deficiencies are linked to defective signaling.
What methods study signaling?
RNA-seq, phosphoproteomics, live-cell imaging, and CRISPR screens are common methods to study signaling.
What is the difference between signaling and signal transduction?
Signaling is the broader GO term covering the entire process from signal to response, while signal transduction often refers to the molecular relay steps within that process.
Can CRISPR be used to study signaling?
Yes, CRISPR knockout, point-mutation, knock-in, and overexpression models are widely used to dissect signaling pathways.
What is systemic signaling in plants?
Systemic signaling in plants involves long-distance transmission of defense signals such as salicylic acid to confer systemic acquired resistance.
How does calcium signaling crosstalk with immune receptors?
Pattern-recognition receptor activation triggers calcium influx, which amplifies and shapes downstream immune responses.
Why is TGF-beta signaling important in cancer?
TGF-beta signaling remodels the tumor microenvironment and can promote immune evasion, making it a therapeutic target.
Conclusion
GO:0023052 (signaling) is a foundational biological process that spans receptor activation, second messenger generation, kinase cascades, and cellular responses. Its dysregulation is central to cancer, immune disorders, and developmental defects, while its study in plants informs crop immunity. CRISPR-based models provide the causal resolution needed to move from correlation to mechanism in signaling research.
References
- 1. Kachroo P et al.. 2020. Salicylic acid: transport and long-distance immune signaling.. Curr Opin Virol 42:53-57 PMID: 32544865
- 2. Nagata S. 2018. Apoptosis and Clearance of Apoptotic Cells.. Annu Rev Immunol 36:489-517 PMID: 29400998
- 3. Jansen M et al.. 2022. How palmitoylation affects trafficking and signaling of membrane receptors.. Biol Cell 114(2):61-72 PMID: 34738237
- 4. Zhao H et al.. 2020. Roles of TGF-β signaling pathway in tumor microenvirionment and cancer therapy.. Int Immunopharmacol 89(Pt B):107101 PMID: 33099067
- 5. Kachroo A et al.. 2013. Systemic signaling during plant defense.. Curr Opin Plant Biol 16(4):527-33 PMID: 23870750
- 6. Holt AL et al.. 2014. Signaling in shoot and flower meristems of Arabidopsis thaliana.. Curr Opin Plant Biol 17:96-102 PMID: 24507500
- 7. Kong F et al.. 2021. The crosstalk between pattern-recognition receptor signaling and calcium signaling.. Int J Biol Macromol 192:745-756 PMID: 34634335
- 8. Dantonio PM et al.. 2018. Exploring major signaling cascades in melanomagenesis: a rationale route for targetted skin cancer therapy.. Biosci Rep 38(5) PMID: 30166456
