GO:0043184 vascular endothelial growth factor receptor 2 binding: Mechanism, Genes and Research Methods
Research-grade guide for scientists and biopharma professionals
Key Takeaways
• GO:0043184 describes the molecular function of selectively binding to vascular endothelial growth factor receptor 2 (VEGFR-2/KDR/Flk-1), a core event in VEGF-driven angiogenesis.
• VEGFR-2 is the principal signaling receptor for VEGF-A and VEGF-E, and its activation controls endothelial proliferation, migration, permeability, and survival.
• Ligand binding to VEGFR-2 triggers receptor dimerization, autophosphorylation, and downstream signaling through PLCγ, PI3K/AKT, and MAPK pathways.
• VEGFR-2 binding is modulated by co-receptors, sialylation, extracellular matrix interactions, and circulating proteins such as transglutaminase 2 and coagulation factor XI.
• Dysregulated VEGFR-2 binding contributes to cancer angiogenesis, inflammatory bowel disease, preeclampsia, and vascular barrier dysfunction.
• Therapeutic antibodies and bispecific molecules that block VEGFR-2 binding are actively developed for anti-angiogenic and anti-tumor strategies.
Description
Vascular endothelial growth factor receptor 2 binding (GO:0043184) is a molecular function that defines the selective interaction between a ligand or protein and VEGFR-2, also known as KDR, Flk-1, or kinase domain region. This binding event is the initiating step of the canonical VEGF signaling axis, which governs endothelial cell behavior during angiogenesis, vascular permeability, and homeostasis. Because VEGFR-2 is the major transducer of pro-angiogenic signals, its binding properties are central to developmental biology, tumor progression, and vascular disease research. The term is distinct from generic receptor binding because it specifies the VEGFR-2 target, reflecting the unique signaling and ligand specificity of this receptor. Researchers study GO:0043184 to understand how extracellular cues are converted into intracellular signals and to design therapeutics that modulate angiogenesis.
vascular endothelial growth factor receptor 2 binding At A Glance
| GO ID | GO:0043184 |
|---|---|
| GO term | vascular endothelial growth factor receptor 2 binding |
| Ontology | molecular_function |
| Synonym | Flk-1 binding; KDR binding; kinase domain region binding; VEGFR 2 binding; VEGF receptor 2 binding |
| Major function | Selective binding to VEGFR-2, initiating receptor dimerization and downstream angiogenic signaling |
| Primary ligands | VEGF-A, VEGF-E, and other VEGFR-2-specific ligands |
| Cellular context | Endothelial cells, pericytes, and tumor-associated vasculature |
| Disease relevance | Cancer, inflammatory bowel disease, preeclampsia, vascular permeability disorders |
What Is GO:0043184?
GO:0043184 is defined by QuickGO as the binding to vascular endothelial growth factor receptor 2. In practical terms, it is the molecular function of a protein or ligand physically and selectively interacting with VEGFR-2 (KDR/Flk-1), as opposed to other VEGF receptors. This function is typically measured by co-immunoprecipitation, surface plasmon resonance, or receptor phosphorylation assays, and it is the first step in VEGFR-2 activation.
Why Is vascular endothelial growth factor receptor 2 binding Important in Cell Biology?
GO:0043184 is important because VEGFR-2 binding is the rate-limiting step for VEGF-driven angiogenesis, a process required for tumor growth, wound healing, and embryonic development. Dysregulated VEGFR-2 binding is implicated in pathological angiogenesis, vascular leak, and inflammation, making it a major therapeutic target. Understanding this binding function at molecular resolution enables the design of antibodies, bispecifics, and small molecules that selectively block or modulate VEGFR-2 signaling.
• Controls endothelial cell proliferation, migration, and survival during angiogenesis.
• Regulates vascular permeability and barrier function in health and disease.
• Is the primary target of anti-angiogenic cancer therapies, including monoclonal antibodies and bispecifics.
• Contributes to inflammatory angiogenesis in conditions such as inflammatory bowel disease.
• Is associated with pregnancy complications such as preeclampsia through altered VEGFR-2 protein interactions.
• Modulated by post-translational modifications such as sialylation, which affect ligand binding and signaling.
• Serves as a biomarker and functional readout in endothelial biology and drug discovery.
• Provides a paradigm for understanding receptor tyrosine kinase binding specificity and signal initiation.
Molecular Mechanism of vascular endothelial growth factor receptor 2 binding
Ligand recognition and binding specificity
In simple terms: This step is about how VEGF ligands find and stick to VEGFR-2.
VEGFR-2 binding is initiated by the selective recognition of ligands such as VEGF-A and VEGF-E by the extracellular immunoglobulin-like domains of VEGFR-2. This interaction is highly specific, distinguishing VEGFR-2 from VEGFR-1 and VEGFR-3, and is governed by structural determinants in both the ligand and receptor. The binding affinity and kinetics determine the strength and duration of downstream signaling.
Receptor dimerization and autophosphorylation
In simple terms: Once a ligand binds, two receptor molecules pair up and activate each other.
Ligand binding induces VEGFR-2 dimerization, which brings the intracellular kinase domains into proximity and enables trans-autophosphorylation of tyrosine residues. These phosphorylated tyrosines serve as docking sites for adaptor proteins and enzymes, propagating the signal. This step is a hallmark of receptor tyrosine kinase activation and is essential for angiogenic signaling.
Downstream signaling cascades
In simple terms: Activated VEGFR-2 turns on multiple cellular switches that drive blood vessel growth.
Phosphorylated VEGFR-2 recruits and activates PLCγ, PI3K/AKT, and MAPK pathways, leading to endothelial cell proliferation, migration, and survival. These cascades also regulate vascular permeability through junctional remodeling and nitric oxide production. The balance between these pathways determines the functional outcome of VEGFR-2 binding.
Modulation by co-receptors and post-translational modifications
In simple terms: Other proteins and sugar modifications can change how well VEGFR-2 binds its ligands.
VEGFR-2 binding is modulated by co-receptors such as neuropilin-1 and by post-translational modifications including sialylation, which can alter ligand affinity and signaling output. Extracellular matrix components and circulating factors such as transglutaminase 2 and coagulation factor XI also influence VEGFR-2-dependent endothelial responses. These layers of regulation fine-tune angiogenesis in different physiological contexts.
Key Genes Involved in GO:0043184 vascular endothelial growth factor receptor 2 binding
The following genes and proteins are central to VEGFR-2 binding and its downstream biology.
| Gene | Major Role | Research Relevance |
|---|---|---|
| KDR (VEGFR-2) | Receptor tyrosine kinase that binds VEGF ligands | Primary target for anti-angiogenic therapy and functional studies |
| VEGFA | Major ligand for VEGFR-2 | Key regulator of angiogenesis and vascular permeability |
| VEGFE | Viral VEGF homolog with selective VEGFR-2 binding | Used to study VEGFR-2-specific signaling |
| FLT1 (VEGFR-1) | Decoy/regulatory receptor for VEGF | Modulates VEGFR-2 availability and signaling |
| NRP1 | Co-receptor enhancing VEGFR-2 binding | Influences ligand presentation and signaling specificity |
| TGM2 | Transglutaminase 2, modulates VEGFR-2 pathway | Linked to inflammatory angiogenesis |
| F11 (Factor XI) | Coagulation factor regulating endothelial permeability | Interacts with VEGFR-2 signaling in barrier function |
| PLCG1 | Downstream effector of VEGFR-2 | Mediates proliferation and migration signals |
| PIK3CA | PI3K catalytic subunit in AKT pathway | Survival and migration signaling downstream of VEGFR-2 |
| MAPK1 | ERK2 kinase in MAPK cascade | Proliferation signaling downstream of VEGFR-2 |
| AKT1 | Serine/threonine kinase in survival pathway | Promotes endothelial survival and angiogenesis |
| SRC | Non-receptor tyrosine kinase | Modulates VEGFR-2 signaling and permeability |
| PTPN11 | Protein tyrosine phosphatase SHP-2 | Regulates VEGFR-2 phosphorylation and signaling |
| CDH5 (VE-cadherin) | Endothelial junctional protein | Links VEGFR-2 signaling to barrier function |
| NOS3 (eNOS) | Endothelial nitric oxide synthase | Mediates VEGFR-2-dependent vasodilation and permeability |
| HIF1A | Hypoxia-inducible factor 1-alpha | Drives VEGFA expression and angiogenesis |
| ANGPT2 | Angiopoietin-2 | Modulates vascular remodeling with VEGFR-2 |
| PDGFRB | Pericyte receptor | Coordinates vessel stabilization with VEGFR-2 signaling |
How Is vascular endothelial growth factor receptor 2 binding Regulated?
VEGFR-2 binding is regulated at multiple levels, including ligand availability, receptor expression, co-receptor interactions, and post-translational modifications such as sialylation. Hypoxia via HIF1A increases VEGFA expression, indirectly enhancing VEGFR-2 binding. Circulating factors like transglutaminase 2 and coagulation factor XI can modulate VEGFR-2-dependent endothelial responses, linking hemostasis and inflammation to angiogenesis. Additionally, phosphatases such as PTPN11 fine-tune the duration and intensity of VEGFR-2 phosphorylation.
vascular endothelial growth factor receptor 2 binding and Human Disease
| Gene | Disease / Biology | Potential Experimental Model |
|---|---|---|
| KDR | Tumor angiogenesis, therapeutic resistance | Endothelial cell KO and point-mutation models |
| TGM2 | Inflammatory bowel disease | TGM2 knockout mice and endothelial co-culture |
| F11 | Vascular permeability disorders | Factor XI knockout and overexpression models |
| VEGFA | Preeclampsia, cancer | Placental organoids and VEGF-A knock-in models |
| NRP1 | Angiogenesis modulation | NRP1 knockout endothelial cells |
Cancer and tumor angiogenesis
VEGFR-2 binding is a driver of tumor angiogenesis, supplying oxygen and nutrients to growing tumors. Blocking this interaction with antibodies or bispecific molecules is a validated anti-cancer strategy. Resistance to VEGFR-2-targeted therapies remains a challenge, motivating structural and functional studies.
Inflammatory bowel disease
Transglutaminase 2 modulates inflammatory angiogenesis via the VEGFR-2 pathway, contributing to disease pathology in inflammatory bowel disease. Targeting VEGFR-2 binding may reduce pathological angiogenesis in chronic inflammation.
Preeclampsia and pregnancy complications
Proteomic studies of VEGFR-2 in human placentas reveal protein associations with preeclampsia, diabetes, gravidity, and labor, suggesting that altered VEGFR-2 binding contributes to placental vascular dysfunction.
Vascular permeability and barrier function
Coagulation factor XI regulates endothelial cell permeability and barrier function in vitro and in vivo, in part through VEGFR-2-dependent mechanisms. Dysregulated VEGFR-2 binding can lead to vascular leak and edema in inflammatory and ischemic conditions.
From vascular endothelial growth factor receptor 2 binding-Related Genes to Experimental Models
| Research Question | Suitable Model |
|---|---|
| Does loss of VEGFR-2 binding abolish angiogenesis? | KDR knockout endothelial cells or zebrafish |
| How do point mutations in the VEGFR-2 kinase domain affect signaling? | Point-mutation knock-in models |
| Can a tagged VEGFR-2 reveal binding partners? | Tagged knock-in (e.g., GFP or HA) |
| Does overexpression of VEGFA drive pathological angiogenesis? | VEGFA overexpression transgenic models |
| What is the role of TGM2 in VEGFR-2-dependent inflammation? | TGM2 knockout and overexpression in IBD models |
| How does factor XI modulate endothelial permeability? | F11 knockout and overexpression models |
How to Study the vascular endothelial growth factor receptor 2 binding Process
| Method | What It Measures | Typical Application |
|---|---|---|
| Co-immunoprecipitation | Physical interaction between VEGFR-2 and partners | Identifying novel binding proteins |
| Surface plasmon resonance | Binding affinity and kinetics | Characterizing ligand-receptor interactions |
| Phospho-immunoblotting | VEGFR-2 activation status | Functional validation of binding |
| Proteomics | VEGFR-2-associated protein complexes | Disease biomarker discovery |
| Immunofluorescence | Subcellular localization of VEGFR-2 | Endothelial cell imaging |
| Endothelial permeability assays | Barrier function changes | Vascular biology studies |
| CRISPR knockout | Loss-of-function phenotypes | Causal gene validation |
| RNA-seq | Transcriptional changes downstream of VEGFR-2 | Pathway analysis |
Co-immunoprecipitation and pull-down assays
These methods detect physical binding between VEGFR-2 and candidate ligands or proteins, providing direct evidence for GO:0043184. They are often combined with mass spectrometry to identify novel binding partners.
Surface plasmon resonance and biophysical binding assays
SPR and related techniques measure binding affinity, kinetics, and specificity between VEGFR-2 and its ligands, informing structural and therapeutic studies.
Phospho-VEGFR-2 immunoblotting and signaling assays
Measuring VEGFR-2 phosphorylation and downstream effectors (PLCγ, AKT, MAPK) confirms functional binding and activation.
Proteomic profiling of VEGFR-2 complexes
Proteomic studies in human placentas have revealed VEGFR-2 protein associations with preeclampsia and other conditions, demonstrating the utility of unbiased approaches.
How CRISPR Can Be Used to Study GO:0043184 vascular endothelial growth factor receptor 2 binding
Knockout
CRISPR knockout of KDR or its ligands ablates VEGFR-2 binding and downstream signaling, providing causal evidence for its role in angiogenesis and permeability. Knockout endothelial cells are widely used to study compensatory pathways and drug resistance.
Point Mutation
Point mutations in the VEGFR-2 kinase domain or ligand-binding interface can dissect specific residues required for binding and activation, revealing structure-function relationships. Such models help explain resistance mutations in clinical settings.
Knock-in
Knock-in of tagged VEGFR-2 (e.g., GFP, HA) enables real-time tracking and interactome analysis in native contexts. Knock-in of disease-associated variants can model altered binding in preeclampsia or cancer.
Overexpression
Overexpression of VEGFA or VEGFR-2 in endothelial or tumor cells enhances angiogenic signaling and can model pathological angiogenesis. Overexpression models are useful for testing anti-VEGFR-2 therapeutics.
How EDITGENE Supports vascular endothelial growth factor receptor 2 binding Research
Researchers studying vascular endothelial growth factor receptor 2 binding-related genes often need to determine whether a candidate gene is causally involved in angiogenesis, permeability, or disease progression. EDITGENE provides the CRISPR tools and services to build precisely engineered cell models that answer these questions.
Contact EDITGENE today to design your custom CRISPR model for vascular endothelial growth factor receptor 2 binding research.
Frequently Asked Questions About vascular endothelial growth factor receptor 2 binding
What is vascular endothelial growth factor receptor 2 binding?
It is the molecular function defined by GO:0043184, describing the selective binding of a protein or ligand to VEGFR-2 (KDR/Flk-1), initiating angiogenic signaling.
What genes are involved in VEGFR-2 binding?
Key genes include KDR (VEGFR-2), VEGFA, VEGFE, NRP1, TGM2, F11, and downstream effectors such as PLCG1, PIK3CA, and MAPK1.
What is the GO ID for VEGFR-2 binding?
The GO ID is GO:0043184, under the molecular_function ontology.
How does VEGFR-2 binding lead to angiogenesis?
Ligand binding induces VEGFR-2 dimerization and autophosphorylation, activating PLCγ, PI3K/AKT, and MAPK pathways that drive endothelial proliferation, migration, and survival.
What diseases are associated with VEGFR-2 binding?
Cancer, inflammatory bowel disease, preeclampsia, and vascular permeability disorders are linked to dysregulated VEGFR-2 binding.
What are the synonyms of GO:0043184?
Synonyms include Flk-1 binding, KDR binding, kinase domain region binding, VEGFR 2 binding, and VEGF receptor 2 binding.
How can I study VEGFR-2 binding in the lab?
Common methods include co-immunoprecipitation, surface plasmon resonance, phospho-immunoblotting, and proteomics.
What CRISPR models are useful for VEGFR-2 binding research?
Knockout, point mutation, knock-in, and overexpression models of KDR and its ligands are widely used.
Is VEGFR-2 binding a therapeutic target?
Yes, antibodies and bispecific molecules targeting VEGFR-2 binding are in development for cancer and angiogenesis-related diseases.
What is the role of sialylation in VEGFR-2 binding?
Sialylation of VEGFR-2 contributes to angiogenesis by modulating receptor function and ligand interactions.
Conclusion
GO:0043184 vascular endothelial growth factor receptor 2 binding is a central molecular function in angiogenesis, integrating ligand recognition, receptor activation, and downstream signaling. Its dysregulation underlies cancer, inflammatory, and pregnancy-related vascular pathologies, making it a prime therapeutic target. Advances in CRISPR modeling and proteomics continue to refine our understanding of this binding event and its translational potential.
References
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- 2. Zhou G et al.. 2026. Transglutaminase 2 modulates inflammatory angiogenesis via vascular endothelial growth factor receptor 2 pathway in inflammatory bowel disease.. J Adv Res 82:751-764 PMID: 40619121
- 3. Cui X et al.. 2021. A Novel Bispecific Antibody Targeting PD-L1 and VEGF With Combined Anti-Tumor Activities.. Front Immunol 12:778978 PMID: 34925354
- 4. Puy C et al.. 2024. Coagulation factor XI regulates endothelial cell permeability and barrier function in vitro and in vivo.. Blood 144(17):1821-1833 PMID: 39158072
- 5. Shah FH et al.. 2025. Targeting vascular endothelial growth receptor-2 (VEGFR-2): structural biology, functional insights, and therapeutic resistance.. Arch Pharm Res 48(5):404-425 PMID: 40341988
- 6. Chiodelli P et al.. 2017. Contribution of vascular endothelial growth factor receptor-2 sialylation to the process of angiogenesis.. Oncogene 36(47):6531-6541 PMID: 28783175
- 7. Lee SH. 2011. Tanibirumab (TTAC-0001): a fully human monoclonal antibody targets vascular endothelial growth factor receptor 2 (VEGFR-2).. Arch Pharm Res 34(8):1223-6 PMID: 21910042
- 8. Ho SJ et al.. 2024. Proteomic studies of VEGFR2 in human placentas reveal protein associations with preeclampsia, diabetes, gravidity, and labor.. Cell Commun Signal 22(1):221 PMID: 38594674
