VEGFR-2/Flk-1 (native), soluble Active Protein | VEGFR-2/Flk-1 active protein
Mouse VEGFR-2/Flk-1 (native), soluble
NCBI and Uniprot Product Information
Uniprot Description
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, may function as decoy receptors for VEGFA, VEGFC and/or VEGFD. Isoform 2 plays an important role as a negative regulator of VEGFA- and VEGFC-mediated lymphangiogenesis by limiting the amount of free VEGFA and/or VEGFC and by 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. Ref.4 Ref.6 Ref.7 Ref.9 Ref.13 Ref.15 Ref.16 Ref.17
Catalytic activity: ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate. Ref.10
Enzyme regulation: 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. May be regulated by hydrogen sulfide (H2S) levels via a sensitive intracellular disulfide bond
By similarity.
Subunit structure: Homodimer in the presence of bound dimeric VEGFA, VEGFC or VEGFD ligands; monomeric in the absence of bound ligands. Can also form heterodimers with FLT1/VEGFR1 and FLT4/VEGFR2. Interacts (tyrosine phosphorylated) with LFYN, NCK1, PLCG1. Interacts (tyrosine-phosphorylated active form preferentially) with DAB2IP (via C2 domain and active form preferentially); the interaction occurs at the late phase of VEGFA response and inhibits KDR/VEGFR2 activity. Interacts with SHBSH2D2A/TSAD, GRB2, MYOF, CBL and PDCD6. Ref.1 Ref.4 Ref.6 Ref.10 Ref.11 Ref.12 Ref.13 Ref.14
Subcellular location: Cell junction. Note: Localized with RAP1A at cell-cell junctions. Ref.4 Ref.13 Ref.15Isoform 1: Cell membrane; Single-pass type I membrane protein. Cytoplasm
By similarity. Nucleus
By similarity. Cytoplasmic vesicle
By similarity. Early endosome
By similarity. Note: 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
By similarity. Ref.4 Ref.13 Ref.15Isoform 2: Secreted Ref.4 Ref.13 Ref.15.
Tissue specificity: Expressed in endothelial cells (at protein level). Detected in embryonic endothelial cells, as well as hematopoietic stem and progenitor cells. Detected in vascular endothelium. Expressed at high levels in adult heart, lung, kidney, brain and skeletal muscle, but is also expressed at lower levels in most other adult tissues. Ref.2 Ref.3 Ref.6 Ref.15
Developmental stage: Expressed in endothelial cells of allantois/umbilical vessels at 8.5 dpc (at protein level). Increases moderately during pregnancy (maximum 2.7-fold at 19 days), and increases further during lactation (maximum 3.7-fold increase on day 7). Ref.8 Ref.15
Domain: The second and third Ig-like C2-type (immunoglobulin-like) domains are sufficient for VEGFC binding
By similarity.
Post-translational modification: N-glycosylated
By similarity.Ubiquitinated. Tyrosine phosphorylation of the receptor promotes its poly-ubiquitination, leading to its degradation via the proteasome or lysosomal proteases
By similarity. Ref.13Autophosphorylated 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-949 is important for interaction with SH2D2A/TSAD and VEGFA-mediated reorganization of the actin cytoskeleton. Phosphorylation at Tyr-1173 is important for interaction with PLCG1 and SHB. Phosphorylation at Tyr-1212 is important for interaction with NCK1 and FYN. Dephosphorylated by PTPRJ at Tyr-799, Tyr-949, Tyr-994, Tyr-1052, Tyr-1057, Tyr-1173 and Tyr-1212
By similarity. Ref.6 Ref.9 Ref.13The inhibitory disulfide bond between Cys-1022 and Cys-1043 may serve as a specific molecular switch for H2S-induced modification that regulates VEGFR2 function
By similarity.
Disruption phenotype: Embryonic lethality at 8.5 to 9.5 dpc, due to early defects in the development of hematopoietic and endothelial cells, leading to defects in vasculogenesis and endocardium development. At 7.5 dpc, there are no blood islands in the yolk sac. Organized blood vessels are absent in the yolk sac and in the embryo. Ref.7
Sequence similarities: Belongs to the protein kinase superfamily. Tyr protein kinase family. CSF-1/PDGF receptor subfamily.Contains 7 Ig-like C2-type (immunoglobulin-like) domains.Contains 1 protein kinase domain.
Research Articles on VEGFR-2/Flk-1
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Product Notes
The VEGFR-2/Flk-1 kdr (Catalog #AAA691714) is an Active Protein produced from Insect Cells and is intended for research purposes only. The product is available for immediate purchase. The Mouse VEGFR-2/Flk-1 (native), soluble reacts with Mouse and may cross-react with other species as described in the data sheet. The amino acid sequence is listed below: ASVGLTGDFL HPPKLSTQKD ILTILANTTL QITCRGQRDL DWLWPNAQRD SEERVLVTEC GGGDSIFCKT LTIPRVVGND TGAYKCSYRD VDIASTVYVY VRDYRSPFIA SVSDQHGIVY ITENKNKTVV IPCRGSISNL NVSLCARYPE KRFVPDGNRI SWDSEIGFTL PSYMISYAGM VFCEAKINDE TYQSIMYIVV VVGYRIYDVI LSPPHEIELS AGEKLVLNCT ARTELNVGLD FTWHSPPSKS HHKKIVNRDV KPFPGTVAKM FLSTLTIESV TKSDQGEYTC VASSGRMIKR NRTFVRVHTK PFIAFGSGMK SLVEATVGSQ VRIPVKYLSY PAPDIKWYRN GRPIESNYTM IVGDELTIME VTERDAGNYT VILTNPISME KQSHMVSLVV NVPPQIGEKA LISPMDSYQY GTMQTLTCTV YANPPLHHIQ WYWQLEEACS YRPGQTSPYA CKEWRHVEDF QGGNKIEVTK NQYALIEGKN KTVSTLVIQA ANVSALYKCE AINKAGRGER VISFHVIRGP EITVQPAAQP TEQESVSLLC TADRNTFENL TWYKLGSQAT SVHMGESLTP VCKNLDALWK LNGTMFSNST NDILIVAFQN ASLQDQGDYV CSAQDKKTKK RHCLVKQLII LGMEASLGDR IAMP. It is sometimes possible for the material contained within the vial of "VEGFR-2/Flk-1 (native), soluble, Active Protein" to become dispersed throughout the inside of the vial, particularly around the seal of said vial, during shipment and storage. We always suggest centrifuging these vials to consolidate all of the liquid away from the lid and to the bottom of the vial prior to opening. Please be advised that certain products may require dry ice for shipping and that, if this is the case, an additional dry ice fee may also be required.Precautions
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