KDR
GeneName
KDR
Summary
KDR, also known as VEGFR2 or Flk-1, is a 152kDa transmembrane receptor that plays a pivotal role in angiogenesis and vascular development. It is predominantly expressed in endothelial cells and localised to the plasma membrane, where it functions as a receptor for vascular endothelial growth factor (VEGF). KDR is involved in various biological processes, including blood vessel formation, endothelial cell differentiation, and cell migration, particularly in response to VEGF stimuli. Additionally, it participates in signalling pathways that regulate cell proliferation and survival, making it essential for maintaining vascular integrity and function.
Importance
KDR is relevant to: - Angiogenesis and tumour growth, as it mediates the effects of VEGF in promoting blood vessel formation in tumours - Cardiovascular diseases, where its dysregulation can lead to pathological angiogenesis - Tissue regeneration and wound healing due to its role in endothelial cell migration and proliferation - Developmental biology, particularly in processes like embryonic hemopoiesis and organogenesis - Targeting in cancer therapies, where inhibiting KDR can disrupt tumour vasculature and hinder tumour growth
Top Products
For researchers investigating KDR, we recommend two excellent primary antibodies. The first is the well-cited polyclonal antibody, Anti-VEGF Receptor 2 antibody (ab2349), which has garnered 153 citations, highlighting its reliability in immunohistochemistry (IHC). This antibody is a trusted choice for those focusing on KDR in tissue samples. Additionally, we offer the recombinant antibody, Anti-VEGF Receptor 2 antibody [EPRER16Y] (ab134191), which is validated for use in Western blotting (WB) and ELISA. With 35 citations, this recombinant product ensures batch-to-batch consistency, making it an ideal option for researchers requiring dependable results in their studies of KDR. The Recombinant human VEGF Receptor 2 protein (Active) ELISA Kit (ab281825) is an excellent option for researchers looking to study KDR in their experiments.
Abcam Product Citation Summary
The data indicates that KDR antibodies are primarily used in studies related to angiogenesis, endothelial cell apoptosis, and vascular health. The applications span various techniques including Western blotting, immunofluorescence, and immunohistochemistry, highlighting the versatility of these antibodies in different experimental contexts.
Abcam Product Citation Table
Domain
The second and third Ig-like C2-type (immunoglobulin-like) domains are sufficient for VEGFC binding.
Function
Tyrosine-protein kinase that acts as a cell-surface receptor for VEGFA, VEGFC and VEGFD. Plays an essential role in the regulation of angiogenesis, vascular development, vascular permeability, and embryonic hematopoiesis. Promotes proliferation, survival, migration and differentiation of endothelial cells. Promotes reorganization of the actin cytoskeleton. Isoforms lacking a transmembrane domain, such as isoform 2 and isoform 3, may function as decoy receptors for VEGFA, VEGFC and/or VEGFD. Isoform 2 plays an important role as negative regulator of VEGFA- and VEGFC-mediated lymphangiogenesis by limiting the amount of free VEGFA and/or VEGFC and preventing their binding to FLT4. Modulates FLT1 and FLT4 signaling by forming heterodimers. Binding of vascular growth factors to isoform 1 leads to the activation of several signaling cascades. Activation of PLCG1 leads to the production of the cellular signaling molecules diacylglycerol and inositol 1,4,5-trisphosphate and the activation of protein kinase C. Mediates activation of MAPK1/ERK2, MAPK3/ERK1 and the MAP kinase signaling pathway, as well as of the AKT1 signaling pathway. Mediates phosphorylation of PIK3R1, the regulatory subunit of phosphatidylinositol 3-kinase, reorganization of the actin cytoskeleton and activation of PTK2/FAK1. Required for VEGFA-mediated induction of NOS2 and NOS3, leading to the production of the signaling molecule nitric oxide (NO) by endothelial cells. Phosphorylates PLCG1. Promotes phosphorylation of FYN, NCK1, NOS3, PIK3R1, PTK2/FAK1 and SRC.
Involvement in disease
Hemangioma, capillary infantile
HCI
A condition characterized by dull red, firm, dome-shaped hemangiomas, sharply demarcated from surrounding skin, usually presenting at birth or occurring within the first two or three months of life. They result from highly proliferative, localized growth of capillary endothelium and generally undergo regression and involution without scarring.
None
Disease susceptibility is associated with variants affecting the gene represented in this entry.
Plays a major role in tumor angiogenesis. In case of HIV-1 infection, the interaction with extracellular viral Tat protein seems to enhance angiogenesis in Kaposi's sarcoma lesions.
Post-translational modifications
N-glycosylated.
Ubiquitinated. Tyrosine phosphorylation of the receptor promotes its poly-ubiquitination, leading to its degradation via the proteasome or lysosomal proteases.
Autophosphorylated on tyrosine residues upon ligand binding. Autophosphorylation occurs in trans, i.e. one subunit of the dimeric receptor phosphorylates tyrosine residues on the other subunit. Phosphorylation at Tyr-951 is important for interaction with SH2D2A/TSAD and VEGFA-mediated reorganization of the actin cytoskeleton. Phosphorylation at Tyr-1175 is important for interaction with PLCG1 and SHB. Phosphorylation at Tyr-1214 is important for interaction with NCK1 and FYN. Dephosphorylated by PTPRB. Dephosphorylated by PTPRJ at Tyr-951, Tyr-996, Tyr-1054, Tyr-1059, Tyr-1175 and Tyr-1214.
The inhibitory disulfide bond between Cys-1024 and Cys-1045 may serve as a specific molecular switch for H(2)S-induced modification that regulates KDR/VEGFR2 function.
Sequence Similarities
Belongs to the protein kinase superfamily. Tyr protein kinase family. CSF-1/PDGF receptor subfamily.
Tissue Specificity
Detected in cornea (at protein level). Widely expressed.
Cellular localization
- Cell junction
- Endoplasmic reticulum
- Cell membrane
- Localized with RAP1A at cell-cell junctions (By similarity). Colocalizes with ERN1 and XBP1 in the endoplasmic reticulum in endothelial cells in a vascular endothelial growth factor (VEGF)-dependent manner (PubMed:23529610).
- Isoform 1
- Cell membrane
- Single-pass type I membrane protein
- Cytoplasm
- Nucleus
- Cytoplasmic vesicle
- Early endosome
- Detected on caveolae-enriched lipid rafts at the cell surface. Is recycled from the plasma membrane to endosomes and back again. Phosphorylation triggered by VEGFA binding promotes internalization and subsequent degradation. VEGFA binding triggers internalization and translocation to the nucleus.
- Isoform 2
- Secreted
- Isoform 3
- Secreted
Alternative names
CD309, FLK1, VEGFR2, KDR, Vascular endothelial growth factor receptor 2, VEGFR-2, Fetal liver kinase 1, Kinase insert domain receptor, Protein-tyrosine kinase receptor flk-1, FLK-1
Database links
swissprot:P35968 entrezGene:3791 omim:191306
Other research areas
- Immuno-oncology
- Immunology & Infectious Disease