KDR - Vascular endothelial growth factor receptor 2 - human protein (Function)
 
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KDR »  Vascular endothelial growth factor receptor 2   [ EC 2.7.10.1 ]  (VEGFR-2)
 
Protein also known as:  Protein-tyrosine kinase receptor flk-1; CD antigen CD309.
Gene name:  KDR
Entry whose protein(s) existence is based on evidence at protein level
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1 645 3
GENE REF ISO

Function

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Overview 
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.  
22
  • UniProtKB
Isoform  Iso 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.  
23
  • UniProtKB
GO molecular function 
ATP bindingdefinition[GO:0005524]  
1
  • UniProtKB KW
Growth factor bindingdefinition[GO:0019838]  
2
  • BHF-UCL
Hsp90 protein bindingdefinition[GO:0051879]  
1
  • BHF-UCL
Integrin bindingdefinition[GO:0005178]  
1
  • BHF-UCL
Protein bindingdefinition[GO:0005515]  
20
  • IntAct
  • UniProtKB
  • BHF-UCL
Protein tyrosine kinase activitydefinition[GO:0004713]  
1
  • UniProtKB
Receptor signaling protein tyrosine kinase activitydefinition[GO:0004716]  
1
  • BHF-UCL
Transmembrane receptor protein tyrosine kinase activitydefinition[GO:0004714]  
1
  • BHF-UCL
Isoform  Iso 2   Vascular endothelial growth factor bindingdefinition[GO:0038085]  
1
  • BHF-UCL
Vascular endothelial growth factor-activated receptor activitydefinition[GO:0005021]  
5
  • UniProtKB
  • BHF-UCL
GO biological process 
Angiogenesisdefinition[GO:0001525]  
1
  • BHF-UCL
Branching morphogenesis of an epithelial tubedefinition[GO:0048754] silver  
1
  • Ortholog Compara
Calcium ion homeostasisdefinition[GO:0055074] silver  
1
  • Ortholog Compara
Calcium-mediated signaling using intracellular calcium sourcedefinition[GO:0035584]  
1
  • UniProtKB
Cell fate commitmentdefinition[GO:0045165] silver  
1
  • Ortholog Compara
Cell maturationdefinition[GO:0048469] silver  
1
  • Ortholog Compara
Cell migration involved in sprouting angiogenesisdefinition[GO:0002042]  
1
  • Ortholog Curator
Cellular response to vascular endothelial growth factor stimulusdefinition[GO:0035924]  
5
  • UniProtKB
Embryonic hemopoiesisdefinition[GO:0035162]  
1
  • Ortholog Curator
Endothelial cell differentiationdefinition[GO:0045446] silver  
1
  • Ortholog Compara
Endothelium developmentdefinition[GO:0003158]  
1
  • Ortholog Curator
Lung alveolus developmentdefinition[GO:0048286] silver  
1
  • Ortholog Compara
Lymph vessel developmentdefinition[GO:0001945] silver  
1
  • Ortholog Compara
Negative regulation of apoptotic processdefinition[GO:0043066]  
1
  • UniProtKB
Negative regulation of endothelial cell apoptotic processdefinition[GO:2000352]  
1
  • UniProtKB
Ovarian follicle developmentdefinition[GO:0001541] silver  
1
  • Ortholog Compara
Peptidyl-tyrosine autophosphorylationdefinition[GO:0038083]  
1
  • Ortholog Curator
Peptidyl-tyrosine phosphorylationdefinition[GO:0018108]  
2
  • UniProtKB
Positive regulation of angiogenesisdefinition[GO:0045766]  
1
  • UniProtKB
Positive regulation of cell migrationdefinition[GO:0030335]  
2
  • UniProtKB
  • BHF-UCL
Positive regulation of cell proliferationdefinition[GO:0008284]  
2
  • UniProtKB
  • BHF-UCL
Positive regulation of endothelial cell migrationdefinition[GO:0010595]  
1
  • BHF-UCL
Positive regulation of endothelial cell proliferationdefinition[GO:0001938]  
2
  • UniProtKB
  • BHF-UCL
Positive regulation of ERK1 and ERK2 cascadedefinition[GO:0070374]  
1
  • UniProtKB
Positive regulation of focal adhesion assemblydefinition[GO:0051894]  
1
  • BHF-UCL
Positive regulation of MAPK cascadedefinition[GO:0043410]  
1
  • UniProtKB
Positive regulation of mesenchymal cell proliferationdefinition[GO:0002053] silver  
1
  • Ortholog Compara
Positive regulation of nitric-oxide synthase biosynthetic processdefinition[GO:0051770]  
2
  • UniProtKB
Positive regulation of phosphatidylinositol 3-kinase signalingdefinition[GO:0014068]  
1
  • UniProtKB
Positive regulation of positive chemotaxisdefinition[GO:0050927]  
1
  • BHF-UCL
Positive regulation of protein phosphorylationdefinition[GO:0001934]  
1
  • UniProtKB
Positive regulation of vasculogenesisdefinition[GO:2001214]  
1
  • Ortholog Curator
Protein autophosphorylationdefinition[GO:0046777]  
3
  • UniProtKB
Regulation of cell shapedefinition[GO:0008360]  
1
  • BHF-UCL
Signal transduction by phosphorylationdefinition[GO:0023014]  
1
  • GOC
Surfactant homeostasisdefinition[GO:0043129] silver  
1
  • Ortholog Compara
Transmembrane receptor protein tyrosine kinase signaling pathwaydefinition[GO:0007169]  
1
  • PINC
Vascular endothelial growth factor receptor signaling pathwaydefinition[GO:0048010]  
4
  • UniProtKB
Vascular endothelial growth factor signaling pathwaydefinition[GO:0038084]  
7
  • GOC
  • InterPro 2 GO
  • Ortholog Compara
Vasculogenesisdefinition[GO:0001570]  
1
  • Ortholog Curator
Viral processdefinition[GO:0016032]  
1
  • UniProtKB KW
Enzymatic activity 
This protein acts as an enzyme. It is known to catalyze the following reaction
EC 2.7.10.1: ATP + a [protein]-L-tyrosine ADP + a [protein]-L-tyrosine phosphate.  
4
  • UniProtKB
  • PROSITE-ProRule
It is regulated in the following manner
Present in an inactive conformation in the absence of bound ligand. Binding of VEGFA, VEGFC or VEGFD leads to dimerization and activation by autophosphorylation on tyrosine residues. Inhibited by the small molecule PTK inhibitor SU5614 ((3Z)-5-Chloro-3-[(3,5-dimethyl-1H-pyrrol-2-yl)methylene]-1,3-dihydro-2H-indol-2-one). May be regulated by hydrogen sulfide (H(2)S) levels via a H(2)S-sensitive intracellular disulfide bond.  
5
  • UniProtKB
 
More information is available from:
Pathways 
According to KEGG, this protein belongs to the following pathways:
Cytokine-cytokine receptor interaction  hsa04060+3791  
Endocytosis  hsa04144+3791  
Focal adhesion  hsa04510+3791  
VEGF signaling pathway  hsa04370+3791  
According to Reactome, this protein belongs to the following pathways:
EPHA-mediated growth cone collapse  REACT_228063  
Integrin cell surface interactions  REACT_13552  
Neurophilin interactions with VEGF and VEGFR  REACT_12473  
VEGF binds to VEGFR leading to receptor dimerization  REACT_12583  
VEGFA-VEGFR2 Pathway  REACT_228166  
VEGFR2 mediated cell proliferation  REACT_228024  
 

Keywords

Biological process 
Angiogenesis  definition   [KW-0037]
Differentiation  definition   [KW-0221]
Host-virus interaction  definition   [KW-0945]
Molecular function 
Developmental protein  definition   [KW-0217]
Kinase  definition   [KW-0418]
Receptor  definition   [KW-0675]
Transferase  definition   [KW-0808]
Tyrosine-protein kinase  definition   [KW-0829]
Technical term 
Reference proteome  definition   [KW-1185]
 

Further external links

Other
GeneWiki: Kinase_insert_domain_receptor
GenomeRNAi: 3791
PRO: PR:P35968
Chemistry
GuidetoPHARMACOLOGY: 1813