Rabbit anti-Mouse VEGFR-2/Flk-1 (Peptide), soluble Polyclonal Antibody | anti-VEGFR-2/Flk-1 antibody

Rabbit Anti-Mouse VEGFR-2/Flk-1 (Peptide), soluble

Cat. Num. AAA691305

• Gene Names: Kdr; Flk1; Ly73; Flk-1; Krd-1; VEGFR2; VEGFR-2; sVEGFR-2; 6130401C07
• Reactivity: Mouse
• Applications: Western Blot
• Purity: Protein A purified
• Synonyms: VEGFR-2/Flk-1 (Peptide); soluble; Polyclonal Antibody; Rabbit Anti-Mouse VEGFR-2/Flk-1 (Peptide); Anti-mouse endogenous sVEGFR-2/Flk-1; fetal liver kinase; Flk1; Flk-1; Kinase NYK; anti-VEGFR-2/Flk-1 antibody

• Host: Rabbit
• Reactivity: Mouse
• Clonality: Polyclonal
• Isotype: Rabbit IgG
• Purity/Purification: Protein A purified
• Form/Format: lyophilized; PBS, pH 7.2

• Applicable Applications for anti-VEGFR-2/Flk-1 antibody: Western Blot (WB)
• Application Notes: WB: Use 1-5 ug/ml
• Preparation: Produced from sera of rabbits immunised with a peptide of the C-terminal end of native mouse soluble VEGFR-2/Flk-1 (GMEASLGDRIAMP).
• Immunogen: peptide: GMEASLGDRIAMP
• Reconstitution: Centrifuge vial prior to opening. Reconstitute in sterile water to a concentration of 0.1-1.0 mg/ml.
• Preparation and Storage: The lyophilized antibody is stable at room temperature for up to 1 month. The reconstituted antibody is stable for at least two weeks at 2-8°C. Frozen aliquots are stable for at least 6 months when stored at -20°C. AVOID REPEATED FREEZE AND THAW CYCLES!

Testing Data

Related Product Information for anti-VEGFR-2/Flk-1 antibody

Disruption of the precise balance of positive and negative molecular regulators of blood and lymphatic vessel growth can lead to myriad diseases. Although dozens of natural inhibitors of hemangiogenesis have been identified, an endogenous selective inhibitor of lymphatic vessel growth has not to our knowledge been previously described. A splice variant of the gene encoding vascular endothelial growth factor receptor-2 (VEGFR-2) that encodes a secreted form of the protein, designated endogenous soluble VEGFR-2 (esVEGFR-2/KDR) has been described. The endogenous soluble esKDR inhibits developmental and reparative lymphangiogenesis by blocking VEGF-C function. Tissue-specific loss of esKDR in mice induced, at birth, spontaneous lymphatic invasion of the normally alymphatic cornea and hyperplasia of skin lymphatics without affecting blood vasculature. Administration of esKDR inhibited lymphangiogenesis but not hemangiogenesis induced by corneal suture injury or transplantation, enhanced corneal allograft survival and suppressed lymphangioma cellular proliferation. Naturally occurring esKDR thus acts as a molecular uncoupler of blood and lymphatic vessels; modulation of esKDR might have therapeutic effects in treating lymphatic vascular malformations, transplantation rejection and, potentially, tumor lymphangiogenesis and lymphedema. Recombinant mouse esFlk-1 generated by alternative splicing consists of the first 6 Ig-like loops followed by the unique C-terminal end: GMEASLGDRIAMP.

References

1. Shibata et al, BMC Medicine 8 (2010) 2. Albaquerque et al, Nature Med 2009 3. Ebos et al, Mol Cancer Res 2 (2004) 4. Ebos et al, Cancer res 68 (2008).

NCBI and Uniprot Product Information

• NCBI GI #: 549321
• NCBI GeneID: 16542
• UniProt Accession #: P35918; C5H7S5
• NCBI Official Full Name: Vascular endothelial growth factor receptor 2
• NCBI Official Synonym Full Names: kinase insert domain protein receptor
• NCBI Official Symbol: Kdr
• NCBI Official Synonym Symbols: Flk1; Ly73; Flk-1; Krd-1; VEGFR2; VEGFR-2; sVEGFR-2; 6130401C07
• NCBI Protein Information: vascular endothelial growth factor receptor 2; kinase NYK; VEGF receptor-2; fetal liver kinase 1; protein-tyrosine kinase receptor flk-1; vascular endothelial growth factor receptor-2; vascular endothelial growth factor receptor-3; vascular endothelial growth factor receptor- 2; soluble vascular endothelial growth factor receptor 2
• UniProt Protein Name: Vascular endothelial growth factor receptor 2
• UniProt Gene Name: Kdr
• UniProt Synonym Gene Names: Flk-1; Flk1; VEGFR-2; FLK-1
• UniProt Entry Name: VGFR2_MOUSE

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.