Full Name
Kinase Insert Domain Receptor
Background
Vascular endothelial growth factor (VEGF) is a major growth factor for endothelial cells. This gene encodes one of the two receptors of the VEGF. This receptor, known as kinase insert domain receptor, is a type III receptor tyrosine kinase. It functions as the main mediator of VEGF-induced endothelial proliferation, survival, migration, tubular morphogenesis and sprouting. The signalling and trafficking of this receptor are regulated by multiple factors, including Rab GTPase, P2Y purine nucleotide receptor, integrin alphaVbeta3, T-cell protein tyrosine phosphatase, etc.. Mutations of this gene are implicated in infantile capillary hemangiomas. [provided by RefSeq, May 2009]
Alternative Names
Alacizumab pegol;934216-54-3;CDP791;g165 DFM-PEG;KDR;kinase insert domain receptor (a type III receptor tyrosine kinase);vascular endothelial growth factor receptor 2;CD309;FLK1;VEGFR;VEGFR2;soluble VEGFR2;fetal liver kinase 1;fetal liver kinase-1;protein
Cellular Localization
Extracellular region or secreted, Plasma membrane, Endosome, Nucleus, Endoplasmic reticulum
Involvement in Disease
Diseases associated with KDR include Hemangioma, Capillary Infantile and Hemangioma.
Related Pathways
Its related pathways are Cell adhesion_Plasmin signaling and Signaling by GPCR.
Function
Tyrosine protein kinase acts as a cell surface receptor for VEGFA, VEGFC and VEGFD. It plays an important role in the regulation of angiogenesis, vascular development, vascular permeability and embryonic hematopoiesis. Promote the proliferation, survival, migration and differentiation of endothelial cells. Promote the reorganization of the actin cytoskeleton. Isomers lacking transmembrane domains, such as Isomer 2 and Isomer 3, may act as decoy receptors for VEGFA, VEGFC, and/or VEGFD. As a negative regulator of VEGFA and VEGFC-mediated lymphangiogenesis, Isoform 2 plays an important role by limiting the amount of free VEGFA and/or VEGFC and preventing them from binding to FLT4. Regulation of FLT1 and FLT4 signals by forming heterodimers. The combination of angiogenesis factor and isoform 1 leads to the activation of multiple signal cascades. The activation of PLCG1 leads to the production of cell signaling molecules triglyceride and inositol 1,4,5-triphosphate and the activation of protein kinase c, which mediates the activation of MAPK1/ERK2, MAPK3/ERK1 and map kinase signaling pathways, and AKT1 signaling Activation of the pathway. Mediates the phosphorylation of PIK3R1, which is the regulatory subunit of phosphatidylinositol 3-kinase, recombines the actin cytoskeleton and activates PTK2/FAK1. The induction of NOS2 and NOS3 mediated by vegfa causes endothelial cells to produce the signal molecule nitric oxide (NO). Phosphorylate PLCG1. Promote the phosphorylation of FYN, NCK1, NOS3, PIK3R1, PTK2/FAK1 and SRC.
Field of research
Cancer antibody; Cell Biology and Cellular Response antibody; Controls and Markers antibody; Developmental Biology antibody; Metabolism antibody; Microbiology and Infectious Disease antibody; Signaling Transduction antibody
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 VEGFR2 function.
Biologic Classification
Protein Based Therapies
Monoclonal antibody (mAb)
Antibody Clone
Alacizumab pegol
Description
Recombinant antibody fragment Fab to VEGF Receptor 2. Alacizumab pegol is an antineoplastic agent. Chemically, it is a pegylated F(ab')2 fragment of a monoclonal antibody.
