Human Vascuar endothelial cell growth factor receptor 3,VEGFR-3/Flt-4 ELISA Kit

Instructions
Code CSB-E04765h
Size 96T,5×96T,10×96T
See More Details 24T ELISA kits trial application
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Product Details

Target Name fms-related tyrosine kinase 4
Alternative Names EC 2.7.10.1 ELISA Kit; flt 4 ELISA Kit; FLT-4 ELISA Kit; FLT4 ELISA Kit; FLT41 ELISA Kit; Fms related tyrosine kinase 4 ELISA Kit; Fms-like tyrosine kinase 4 ELISA Kit; LMPH1A ELISA Kit; PCL ELISA Kit; Soluble VEGFR3 variant 1 ELISA Kit; Soluble VEGFR3 variant 2 ELISA Kit; Soluble VEGFR3 variant 3 ELISA Kit; Tyrosine protein kinase receptor FLT4 ELISA Kit; Tyrosine-protein kinase receptor FLT4 ELISA Kit; Vascular endothelial growth factor receptor 3 ELISA Kit; Vascular endothelial growth factor receptor 3 precursor ELISA Kit; VEGF R3 ELISA Kit; VEGFR 3 ELISA Kit; VEGFR-3 ELISA Kit; VEGFR3 ELISA Kit; VGFR3_HUMAN ELISA Kit
Abbreviation VEGFR-3/Flt-4
Uniprot No. P35916
Species Homo sapiens (Human)
Sample Types serum, plasma, tissue homogenates
Detection Range 0.156 ng/mL-10 ng/mL
Sensitivity 0.039 ng/mL
Assay Time 1-5h
Sample Volume 50-100ul
Detection Wavelength 450 nm
Research Area Signal Transduction
Assay Principle quantitative
Measurement Sandwich
Precision
Intra-assay Precision (Precision within an assay): CV%<8%
Three samples of known concentration were tested twenty times on one plate to assess.
Inter-assay Precision (Precision between assays): CV%<10%
Three samples of known concentration were tested in twenty assays to assess.
Linearity
To assess the linearity of the assay, samples were spiked with high concentrations of human VEGFR-3/Flt-44 in various matrices and diluted with the Sample Diluent to produce samples with values within the dynamic range of the assay.
  Sample Serum(n=4)
1:1 Average % 98
Range % 91-105
1:2 Average % 90
Range % 85-96
1:4 Average % 95
Range % 85-105
1:8 Average % 92
Range % 83-98
Recovery
The recovery of human VEGFR-3/Flt-44 spiked to levels throughout the range of the assay in various matrices was evaluated. Samples were diluted prior to assay as directed in the Sample Preparation section.
Sample Type Average % Recovery Range
Serum (n=5) 95 86-100
EDTA plasma (n=4) 93 87-98
Typical Data
These standard curves are provided for demonstration only. A standard curve should be generated for each set of samples assayed.
ng/ml OD1 OD2 Average Corrected
10 2.549 2.516 2.533 2.420
5 1.517 1.557 1.537 1.424
2.5 0.796 0.758 0.777 0.664
1.25 0.472 0.489 0.481 0.368
0.625 0.302 0.315 0.309 0.196
0.312 0.259 0.246 0.253 0.140
0.156 0.164 0.171 0.168 0.055
0 0.111 0.115 0.113  
Troubleshooting
and FAQs
ELISA kit FAQs
Storage Store at 2-8°C. Please refer to protocol.
Lead Time 3-5 working days

Citations

Target Data

Function Tyrosine-protein kinase that acts as a cell-surface receptor for VEGFC and VEGFD, and plays an essential role in adult lymphangiogenesis and in the development of the vascular network and the cardiovascular system during embryonic development. Promotes proliferation, survival and migration of endothelial cells, and regulates angiogenic sprouting. Signaling by activated FLT4 leads to enhanced production of VEGFC, and to a lesser degree VEGFA, thereby creating a positive feedback loop that enhances FLT4 signaling. Modulates KDR signaling by forming heterodimers. The secreted isoform 3 may function as a decoy receptor for VEGFC and/or VEGFD and play an important role as a negative regulator of VEGFC-mediated lymphangiogenesis and angiogenesis. Binding of vascular growth factors to isoform 1 or isoform 2 leads to the activation of several signaling cascades; isoform 2 seems to be less efficient in signal transduction, because it has a truncated C-terminus and therefore lacks several phosphorylation sites. Mediates activation of the MAPK1/ERK2, MAPK3/ERK1 signaling pathway, of MAPK8 and the JUN signaling pathway, and of the AKT1 signaling pathway. Phosphorylates SHC1. Mediates phosphorylation of PIK3R1, the regulatory subunit of phosphatidylinositol 3-kinase. Promotes phosphorylation of MAPK8 at 'Thr-183' and 'Tyr-185', and of AKT1 at 'Ser-473'.
Gene References into Functions
  1. VEGFR3 has a role in lymphatic vessel hyperplasia through cell-autonomous and non-cell-autonomous mechanisms PMID: 29615616
  2. These results suggest functional interactions among ATX, VEGFR-2, and VEGFR-3 in the modulation of hemovascular and lymphovascular cell activation during vascular development. PMID: 30456868
  3. VEGFR-3 and CAV3 expression demonstrated immunohistochemically in SMCs of the tunica media of SV grafts predicted their early restenosis in triple-vessel CAD patients. CAV2 protein expression in SMCs of ITA grafts indicated the risk of early graft failure both in double-vessel and triple-vessel CAD subjects. PMID: 29557990
  4. Single nucleotide polymorphism of VEGFR3 is associated with relapse in gastroenteropancreatic neuroendocrine neoplasms. PMID: 29787601
  5. VEGFR3 single nucleotide polymorphisms association with lymphedema caused by Wuchereria bancrofti. PMID: 29122006
  6. The results imply a very good sensitivity of VEGFR-3 in ESCC. VEGFR-3 may be a good diagnostic biomarker for ESCC. PMID: 28447586
  7. VEGFR-3 expression was associated with depth of invasion and lymph node metastasis in gastric cancer PMID: 28939099
  8. The finding of rare LAMA5 variants together with FLT4 in Milroy disease suggests that these mutations may be co-responsible for these disorders and most likely interfere with the function of lymphatics. PMID: 29908552
  9. Rare inherited and de novo variants in 2,871 congenital heart disease probands identified GDF1, MYH6, and FLT4 as causative genes. PMID: 28991257
  10. There was a significant decrease in VEGFR3 expression in pulmonary arterial endothelial cells from pulmonary arterial hypertension patients. PMID: 28356442
  11. By treating LECs with VEGF-C156S and analyzing subsequent changes in gene expression, we identified several 'immediate early' transcription factors that showed a rapid transient upregulation VEGFR-3 stimulation. these results reveal an important and unanticipated role of HOXD10 in the regulation of VEGFR-3 signaling in lymphatic endothelial cells, and in the control of lymphangiogenesis and permeability. PMID: 27199372
  12. These results indicate that VEGF-C-induced MSC osteogenesis is mediated through VEGFR2 and VEGFR3, and followed the activation of the ERK/RUNX2 signaling pathway. PMID: 28163024
  13. Assessment of VEGFR-2/VEGFR-3 on tumor samples might serve as a putative prognostic factor in renal cell carcinoma cases, identifying a subset of patients that may benefit from antiangiogenic treatments targeting VEGFR receptors. PMID: 27837630
  14. This study suggests that NRP1 expression and LVD are independent factors that are likely to predict the risk of LN metastasis in squamous cell carcinoma (SCC)of the tongue, whereas the expression of VEGFC, VEGFR3, CCR7, and SEMA3E are nonindependent predictive factors PMID: 27666723
  15. The summarizes the structure and function features of pathway-related molecules of VEGFC/D-VEGFR3/NRP2 axis, stages of various tumors and their molecular mechanisms and significances in tuthe expression changes of these molecules in different anatomic organs or histopathologic types or development lymphatic metastasis. PMID: 27527412
  16. this study uncovers a unique molecular mechanism of lymphangiogenesis in which galectin-8-dependent crosstalk among VEGF-C, podoplanin and integrin pathways plays a key role. PMID: 27066737
  17. Report FLT4 genetic alterations in angiosarcomas. PMID: 26735859
  18. Data indicate that foretinib suppresses angiogenesis and lymphangiogenesis by blocking vascular endothelial growth factor receptors PMID: 25909285
  19. Genistein suppresses FLT4 and inhibits human colorectal cancer metastasis. PMID: 25605009
  20. A Novel Missense Mutation in FLT4 Causes Autosomal Recessive Hereditary Lymphedema PMID: 26091405
  21. Missense mutations in VEGFR3 confirmed Milroy disease in two unrelated patients. PMID: 25896638
  22. Case Reports: novel FLT4 gene mutation in a Chinese family with Milroy disease. PMID: 26714373
  23. TNFR1 has a role in mediating TNF-alpha-induced tumour lymphangiogenesis and metastasis by modulating VEGF-C-VEGFR3 signalling PMID: 25229256
  24. Experiments in mice and zebrafish demonstrate that changing levels of VEGFR3/Flt4 modulates aortic lumen diameter consistent with flow-dependent remodeling PMID: 25643397
  25. VEGFR-3 is a new target to improve net ultrafiltration in methylglyoxal-induced peritoneal injury by suppressing lymphatic absorption PMID: 26121315
  26. the best characterized of these signaling pathways, that involving the vascular endothelial growth factor (VEGF) family members VEGF-C and VEGF-D, together with their receptors VEGFR2 and VEGFR3. PMID: 25399804
  27. Although MYC is a valuable ancillary tool in distinguishing angiosarcomas from atypical vascular lesions , FLT4 immunohistochemistry may be used to screen for patients with FLT4 gene amplification PMID: 25864386
  28. Expression of VEGFR-3 was highly correlated with tumor metastasis in prostate cancer patients. PMID: 24858271
  29. Neuropilin-2 mediates lymphangiogenesis of colorectal carcinoma via a VEGFC/VEGFR3 independent signaling. PMID: 25543087
  30. High CD31 expression associated significantly with better survival and VEGFR3 had no association with survival. Both higher tumor grade and stage were associated with a decreased survival time PMID: 25667475
  31. analysis of how VEGF, VEGFR3, and PDGFRB protein expression is influenced by RAS mutations in medullary thyroid carcinoma PMID: 24754736
  32. VEGFR3 lymphatic endothelium signaling involves regulation of AKT activation via VEGFR3/VEGFR2/neuropilin 1 complex, ERK via VEGFR3/R3 homodimer, as well as regulatory roles of VE-PTP. PMID: 25524775
  33. increased expression in tumors of Ang-2 may individually, or in combination with VEGFR-3, predict poor prognosis of OSCC PMID: 24040410
  34. VEGF-C down-regulates VEGFR-3 in lymphatic endothelial cells PMID: 25281926
  35. Increase of VEGFR3 protein expression is associated with oral squamous cell carcinoma. PMID: 24085575
  36. Data suggest that VEGFC (vascular endothelial growth factor C) enhances cervical cancer invasiveness via up-regulation of galectin-3 via stimulation of NFkappaB/RELA pathway; galectin-3 interacts/activates VEGFR3. PMID: 24650367
  37. The expressions of VEGF-A, VEGFR2 and VEGFR3 were studied in by immunohistochemistry in 76 endometrial carcinoma specimens. VEGFR2 and VEGFR3 receptor expression were also studied by qRT-PCR in 17 tumors in comparison to normal endometrium. PMID: 24845798
  38. The present findings suggest the potential role of VEGF-C in the pathogenesis and development of a pterygium through lymphangiogenesis and the VEGF-C/VEGFR-3 pathway as a novel therapeutic target for the human pterygium. PMID: 22910845
  39. These findings suggest that the VEGFC/VEGFR3 pathway acts as an enhancer of ovarian cancer progression PMID: 24508126
  40. A novel GC-rich element (GRE) spanning -101/-66 sufficient for VEGFR3 transcription and activated by Sp1 and Sp3, respectively, was identified. PMID: 24710631
  41. Case Report: FLT4 missense mutation in Milroy disease. PMID: 25109169
  42. probe F2 facilitated the identification of the target spectrum of the two inhibitors confirming many of the previously identified (off-) targets such as AURKA, FLT4-VEGFR3, IKBKE and PDGFRbeta. PMID: 24184958
  43. The CXCL12-CXCR4 axis may influence the expression of VEGFR3 in urothelial bladder carcinoma and promote tumor recurrence. PMID: 24982366
  44. In primary ovarian cancer tissue, VEGFR3 expression, detected with an frequency of 26%, was mostly located in the vascular wall and across the stroma. PMID: 24713547
  45. VEGF-C and VEGFR-3 expression was significantly higher in luminal A subtype compared to luminal B. PMID: 24398987
  46. Transwell assays revealed that VEGF-C receptor, VEGFR-3, as well as chemokine CCL21 receptor, CC chemokine receptor 7 (CCR7), were responsible for the migration of PC3 cells toward hypoxia preconditioned MSCs PMID: 23939705
  47. Lymph node and lung metastases of HEC1A cells were completely suppressed by the muscle-mediated expression of sVEGFR-3. PMID: 23614535
  48. unlike an anti-VEGFR-3 Mab (mF4-31C1), DC101 was not capable of eliminating either tumor lymphangiogenesis or lymphogenous metastasis (60 % reduction of lymph node metastasis by DC101 vs 95 % by mF4-31C1). PMID: 23591595
  49. Data suggest that circulating VEGFR3/CD34 are biomarkers for epithelial ovarian cancer (EOC); circulating bone marrow-derived lymphatic/vascular endothelial progenitor cells are significantly increased in EOC and correlate with lymph node metastasis. PMID: 23803010
  50. Binding of VEGF-C and endostatin to recombinant VEGFR-3 is competitive. PMID: 22512651
  51. this data suggest a relationship between VEGFR-3 and IFN-gamma expression in NK cells. PMID: 23404187
  52. Data indicate that mutation of the conserved residues mediating the D5 interaction (Thr446 and Lys516) and the D7 interaction (Arg737) compromised VEGF-C induced VEGFR-3 activation. PMID: 23878260
  53. The rs10085109 single nucleotide polymorphism in the FLT4 gene were associated with susceptibility to atopic dermatitis. PMID: 23490417
  54. malignant and stromal cells express high levels of VEGFR-3 in all stages of MF. PMID: 22946664
  55. Studies indicate that variants in the VEGFR3 (FLT4) gene, encoding vascular endothelial growth factor receptor 3 (VEGFR3), were identified as being responsible for the majority of Milroy disease (MD). PMID: 23074044
  56. NRP2 and VEGFR-3 mRNA levels were significantly higher in some of the vascular malformations endothelial cells. PMID: 22961441
  57. VEGF-D and VEGFR-3 expression was significantly higher in benign prostate tissue compared to tumor in the stroma and the endothelium of lymphatic and blood vessels. PMID: 23038639
  58. The commitment of Prox1 positive cells through a lymphatic lineage is an early event for cervical neoplastic progression, being present starting with intraepithelial cervical lesions, and is strongly associated with VEGFR3 and VEGF-C expression. PMID: 23059885
  59. Shh, Gli1, VEGFC, and VEGFR3 expression was higher in colorectal adenocarcinoma than in normal mucosa. Gli1 expression correlated with VEGFC and VEGFR3 expression but not lymphatic metastasis. PMID: 23336661
  60. ELISA for the quantification of sVEGFR-3 in human plasma was validated and applied in clinical trials. PMID: 22819208
  61. Studies indicate that Vascular endothelial growth factor-C (VEGF-C) and VEGF receptor 3 signaling are essential for the development of lymphatic vessels and is a promising target for inhibition of tumor lymphangiogenesis. PMID: 22179834
  62. VEGFR3 is involved in the induction of lymphangiogenesis which results in lymphatic spread of nasopharyngeal carcinoma. PMID: 22366442
  63. Vascular endothelial growth factor receptor-3 directly interacts with phosphatidylinositol 3-kinase to regulate lymphangiogenesis. PMID: 22745786
  64. Data suggest a regulatory role for VEGFR-3 in megakaryopoiesis. PMID: 22797697
  65. K14-VEGFR-3-Ig transgenic mice lack dermal lymphatic capillaries and experience markedly depressed transport of dendritic cells from the skin to draining lymph nodes. PMID: 22844119
  66. results demonstrate that the proteolytic enzyme MMP-9 promotes resistant epithelial breast cancer cells migration and tubular network formation through VEGFR-2/ VEGFR-3 activation PMID: 22542663
  67. High VEGFR-3 gene expression is associated with lymphatic metastasis in laryngeal squamous cell carcinomas. PMID: 22502683
  68. Single nucleotide polymorphisms in VEGFR3 gene is associated with lymphedema after breast cancer. PMID: 22404826
  69. The recombinant lentivirus particles were able to remarkably suppress VEGFR-3 expression, regulate the cell cycle, inhibit proliferation and induce apoptosis in the MKN45 cell lines. PMID: 21805024
  70. Suggest that miR-1236 may function as a negative regulator of VEGFR-3 signaling during inflammatory lymphangiogenesis. PMID: 22223733
  71. The correlation between VEGFR-3 and the Gleason score was high in prostate cancer. PMID: 21269982
  72. Strong expression of VEGF-C and VEGFR-3 in gastrointestinal stromal tumors was not correlated with the clinical parameters of aggressiveness, nor with high lymphatic vessel density. PMID: 21972089
  73. LYVE-1, VEGFR-3 and CD44 all play an important role in lymphangiogenesis, invasion and metastasis PMID: 21912471
  74. the effects of vegfc/VEGFR3 on the progression of tumor cells to form lymph node metastases occur primarily under an hypoxic tumor microenvironment. PMID: 21839498
  75. Macrophage-derived VEGF-C activates VEGFR-3 in tip cells to reinforce Notch signalling, which contributes to the phenotypic conversion of endothelial cells at fusion points of vessel sprouts. PMID: 21909098
  76. There is a close relationship of laryngeal squamous cell carcinomas with the expression of VEGF-C and VEGFR-3. PMID: 19813623
  77. VEGFR-3 expression was correlated with histological grade, lymph node status and distant metastasis, but not correlated with gender, age, location, tumor size and TNM staging of papillary renal cell carcinoma. PMID: 21163065
  78. RNAi-mediated silencing of VEGF-C inhibits non-small cell lung cancer progression by simultaneously down-regulating the CXCR4, CCR7, VEGFR-2 and VEGFR-3-dependent axes-induced ERK, p38 and AKT signalling pathways. PMID: 21680174
  79. findings show VEGFR-2 and VEGFR-3 expression are markers of a poor prognosis in patients with surgically resected colorectal adenocarcinoma, whereas EGFR has a minor influence PMID: 21635552
  80. As2O3 can inhibit expression of VEGF-C and VEGFR-3 of human gastric cancer xenografts in nude mice. PMID: 19099632
  81. VEGFR-3 is a strong and independent negative prognostic marker for non-GIST STSs with wide resection margins PMID: 21179485
  82. High VEGFR-3 in stromal vessels is associated with gastric cancer. PMID: 19068081
  83. VEGF-C and its receptor FLT-4 play an important role in the lymphatic metastasis of laryngeal and hypopharyngeal squamous cell carcinoma. PMID: 16375119
  84. High-level MYC amplification was found in 100% of secondary Angiosarcoma (AS), but in none of the AVL or other radiation-associated sarcomas. Coamplification of FLT4 (encoding VEGFR3) was identified in 25% of secondary AS, but not in other types. PMID: 20949568
  85. The upregulation of VEGFR-3 on tumor blood vessels indicates a potential additional antiangiogenic effect for dual VEGFR-2/VEGFR-3-targeted therapy. PMID: 20606037
  86. The herein described case, which is the third reported so far with c.3109G>C mutation, adds data on genotypic-phenotypic correlation of Milroy disease PMID: 20555004
  87. The high expressions of VEGF-C/VEGFR-3 and inactivation of nm23-H(1) may play an important role in lymphatic metastasis in oral squamous cell carcinoma. PMID: 18307927
  88. Cell adhesion to extracellular matrix induces a downstream signaling using the tyrosine kinase receptor VEGFR-3 as scaffold. PMID: 20431062
  89. VEGF-C/flt-4 system can promote vasculogenesis in stroma of breast cancer. The number of Flt-4 positive vessels is closely related to lymph node metastasis. PMID: 14558949
  90. There was a close correlation between the expressions of VEGFR-3, CD31 and prostate tumor metastases. PMID: 16044920
  91. Both VEGFA and VEGFC potently induce formation of VEGFR2/-3 heterodimers. PMID: 20224550
  92. co-expression of PDGF-B and VEGFR-3 is strongly associated with poor survival in NSCLC patients. PMID: 19628565
  93. The nuclear localization of VEGF-C and its receptor Flt-4 is a novel finding from this study. It was more common in follicular than in peripheral T-cell or diffuse large-cell lymphomas. High Flt4 correlated with disseminated disease. PMID: 19701853
  94. Data show that tumor spheroid cells express ABCG2, Bmi1, WNT5A, CD133, prox1 and VEGFR3. PMID: 19940551
  95. Stimulation of trophoblasts (BeWo cells) with gal-1 showed a significant alteration of phosphorylation status in 3 receptor tyrosine kinases: JAK2, RET and VEGFR3. Phosphorylation of these kinases could be involved in gal-1-induced cell differentiation. PMID: 19900702
  96. Prox1 synergizes with the p50 of NF-kappaB to control VEGFR-3 expression. PMID: 19901262
  97. A potential mechanism involved in hemangioma formation is the alteration of the FLT4 signaling pathway in endothelial and/or pericytic cells. PMID: 11807987
  98. VEGF-C signaling through FLT-4 (VEGFR-3) mediates leukemic cell proliferation, survival, and resistance to chemotherapy. PMID: 11877295
  99. Suppression of tumor lymphangiogenesis and lymph node metastasis by blocking vascular endothelial growth factor receptor 3 signaling. PMID: 12048269
  100. Vascular endothelial growth factor receptor-3 (VEGFR-3) and its ligand VEGF-C are expressed in human colorectal adenocarcinoma. PMID: 12168824

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Involvement in disease Lymphedema, hereditary, 1A (LMPH1A); Hemangioma, capillary infantile (HCI)
Subcellular Location Cell membrane, Single-pass type I membrane protein, Cytoplasm, Nucleus, Note=Ligand-mediated autophosphorylation leads to rapid internalization, SUBCELLULAR LOCATION: Isoform 1: Cell membrane, Single-pass type I membrane protein
Protein Families Protein kinase superfamily, Tyr protein kinase family, CSF-1/PDGF receptor subfamily
Tissue Specificity Detected in endothelial cells (at protein level). Widely expressed. Detected in fetal spleen, lung and brain. Detected in adult liver, muscle, thymus, placenta, lung, testis, ovary, prostate, heart, and kidney.
Database Links

HGNC: 3767

OMIM: 136352

KEGG: hsa:2324

STRING: 9606.ENSP00000261937

UniGene: Hs.646917

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