Vascular endothelial growth factor receptor 1
Also known as: FLT, FLT1, FRT, VEGFR1
Function
Tyrosine-protein kinase that acts as a cell-surface receptor for VEGFA, VEGFB and PGF, and plays an essential role in the development of embryonic vasculature, the regulation of angiogenesis, cell survival, cell migration, macrophage function, chemotaxis, and cancer cell invasion. Acts as a positive regulator of postnatal retinal hyaloid vessel regression (By similarity). May play an essential role as a negative regulator of embryonic angiogenesis by inhibiting excessive proliferation of endothelial cells. Can promote endothelial cell proliferation, survival and angiogenesis in adulthood. Its function in promoting cell proliferation seems to be cell-type specific. Promotes PGF-mediated proliferation of endothelial cells, proliferation of some types of cancer cells, but does not promote proliferation of normal fibroblasts (in vitro). Has very high affinity for VEGFA and relatively low protein kinase activity; may function as a negative regulator of VEGFA signaling by limiting the amount of free VEGFA and preventing its binding to KDR. Modulates KDR signaling by forming heterodimers with KDR. Ligand binding leads to the activation of several signaling cascades. Activation of PLCG leads to the production of the cellular signaling molecules diacylglycerol and inositol 1,4,5-trisphosphate and the activation of protein kinase C. Mediates phosphorylation of PIK3R1, the regulatory subunit of phosphatidylinositol 3-kinase, leading to activation of phosphatidylinositol kinase and the downstream signaling pathway. Mediates activation of MAPK1/ERK2, MAPK3/ERK1 and the MAP kinase signaling pathway, as well as of the AKT1 signaling pathway. Phosphorylates SRC and YES1, and may also phosphorylate CBL. Promotes phosphorylation of AKT1 at 'Ser-473'. Promotes phosphorylation of PTK2/FAK1.
Classification
- Family (Pfam)
- PF07679 I-set, PF00047 ig, PF13927 Ig_3, PF22971 Ig_VEGFR-1-like_5th, PF07714 PK_Tyr_Ser-Thr, PF21339 VEGFR-1-like_Ig-like, PF17988 VEGFR-2_TMD, PF22854 VEGFR1-3_N_Ig-like
- InterPro
- Ig-like_dom, Ig-like_dom_sf, Ig-like_fold, Ig_I-set, Ig_sub, Ig_sub2, Ig_V-set, Immunoglobulin_dom, Kinase-like_dom_sf, Prot_kinase_dom, Protein_kinase_ATP_BS, RTK, Ser-Thr/Tyr_kinase_cat_dom, Tyr_kinase_AS, Tyr_kinase_cat_dom, Tyr_kinase_rcpt_3_CS, VEGFR-2_TMD, VEGFR1-3_5th, VEGFR1-3_N_Ig-like, VEGFR1_rcpt
- Functional cluster
- Immunoglobulin-Domain Cell Adhesion Proteins
Experimental structures · PDB · 12
- 1FLT X-ray 1.70A
- 1QSV NMR
- 1QSZ NMR
- 1QTY X-ray 2.70A
- 1RV6 X-ray 2.45A
- 2XAC X-ray 2.71A
- 3HNG X-ray 2.70A
- 4CKV X-ray 2.06A
- 4CL7 X-ray 2.00A
- 5ABD X-ray 2.00A
- 5EX3 X-ray 2.41A
- 5T89 X-ray 4.00A
A predicted model is available from AlphaFold.
Gene Ontology · 30
- GO:0005768 endosome
- GO:0005615 extracellular space
- GO:0005925 focal adhesion
- GO:0005886 plasma membrane
- GO:0043235 receptor complex
- GO:0005524 ATP binding
- GO:0019838 growth factor binding
- GO:0036332 placental growth factor receptor activity
- GO:0004714 transmembrane receptor protein tyrosine kinase activity
- GO:0005021 vascular endothelial growth factor receptor activity
- GO:0048514 blood vessel morphogenesis
- GO:0030154 cell differentiation
- GO:0016477 cell migration
- GO:0007169 cell surface receptor protein tyrosine kinase signaling pathway
- GO:0035924 cellular response to vascular endothelial growth factor stimulus
- GO:0048598 embryonic morphogenesis
- GO:1990384 hyaloid vascular plexus regression
- GO:0002548 monocyte chemotaxis
- GO:1905563 negative regulation of vascular endothelial cell proliferation
- GO:0018108 peptidyl-tyrosine phosphorylation
- GO:0045766 positive regulation of angiogenesis
- GO:0030335 positive regulation of cell migration
- GO:0008284 positive regulation of cell population proliferation
- GO:0043406 positive regulation of MAP kinase activity
- GO:0043410 positive regulation of MAPK cascade
- GO:0051897 positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction
- GO:0046777 protein autophosphorylation
- GO:0002040 sprouting angiogenesis
- GO:0048010 vascular endothelial growth factor receptor signaling pathway
- GO:0036323 vascular endothelial growth factor receptor-1 signaling pathway
Drugs targeting this protein · 42
- VATALANIB inhibitor
- SORAFENIB TOSYLATE inhibitor
- PAZOPANIB HYDROCHLORIDE inhibitor
- FORETINIB inhibitor
- FAMITINIB inhibitor
- TIVOZANIB inhibitor
- AXITINIB inhibitor
- CEP-5214 inhibitor
- SUNITINIB MALATE inhibitor
- OSI-930 inhibitor
- SU-014813 inhibitor
- REGORAFENIB inhibitor
- ILORASERTIB inhibitor
- RG-1530 inhibitor
- CEP-11981 inhibitor
- LENVATINIB MESYLATE inhibitor
- TIVOZANIB HYDROCHLORIDE inhibitor
- TAK-593 inhibitor
- LUCITANIB inhibitor
- LINIFANIB inhibitor
- VANDETANIB inhibitor
- BRIVANIB ALANINATE inhibitor
- SEMAXANIB inhibitor
- NINTEDANIB ESYLATE inhibitor
- L-21649 inhibitor
- CEP-7055 inhibitor
- AG-13958 inhibitor
- BMS-690514 inhibitor
- BRIVANIB inhibitor
- GLESATINIB inhibitor
- TG100-801 inhibitor
- KRN-633 inhibitor
- SURUFATINIB inhibitor
- FRUQUINTINIB inhibitor
- CEDIRANIB inhibitor
- IBCASERTIB inhibitor
- DOVITINIB inhibitor
- XL-999 inhibitor
- 4SC-203 inhibitor
- SUNITINIB inhibitor
- MOTESANIB inhibitor
- AEE-788 inhibitor
Related proteins · sequence + function similarity
- Vascular endothelial growth factor receptor 1 0.98
- Vascular endothelial growth factor receptor 1 0.98
- Vascular endothelial growth factor receptor 1 0.97
- Vascular endothelial growth factor receptor 2 0.90
- Vascular endothelial growth factor receptor 3 0.89
- Vascular endothelial growth factor receptor 2 0.89
- Vascular endothelial growth factor receptor 3 0.89
- Vascular endothelial growth factor receptor kdr-like 0.88
- Vascular endothelial growth factor receptor 2 0.88
- Vascular endothelial growth factor receptor 2 0.88
- Vascular endothelial growth factor receptor 2 0.86
- Vascular endothelial growth factor receptor 3 0.85
Co-cited proteins · studied together in the literature
- Vascular endothelial growth factor receptor 2 6 shared papers
- Vascular endothelial growth factor receptor 1 1 shared papers
- Vascular endothelial growth factor receptor 3 4 shared papers
- Vascular endothelial growth factor receptor 2 1 shared papers
- E3 ubiquitin-protein ligase CBL 2 shared papers
- 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1 1 shared papers
- SH2/SH3 adapter protein Nck1 1 shared papers
- Small ribosomal subunit protein RACK1 1 shared papers
- Phosphatidylinositol 3-kinase regulatory subunit beta 1 shared papers
- SH2/SH3 adapter protein NCK1 1 shared papers
- Adapter molecule crk 1 shared papers
- Tyrosine-protein phosphatase non-receptor type 11 1 shared papers
Literature · 43 cited papers
- gamma-Secretase and presenilin mediate cleavage and phosphorylation of vascular endothelial growth factor receptor-1. J. Biol. Chem. · 2011
- Autocrine activity of soluble Flt-1 controls endothelial cell function and angiogenesis. Vasc. Cell · 2011
- Signal transduction by vascular endothelial growth factor receptors. Biochem. J. · 2011
- Involvement of Flt-1 (VEGF receptor-1) in cancer and preeclampsia. Proc. Jpn. Acad., B, Phys. Biol. Sci. · 2011
- RACK1 regulates VEGF/Flt1-mediated cell migration via activation of a PI3-K/Akt pathway. J. Biol. Chem. · 2011
- Placental growth factor (PlGF) enhances breast cancer cell motility by mobilising ERK1/2 phosphorylation and cytoskeletal rearrangement. Br. J. Cancer · 2010
- A novel intracellular isoform of VEGFR-1 activates Src and promotes cell invasion in MDA-MB-231 breast cancer cells. J. Cell. Biochem. · 2010
- Structural insights into the binding of vascular endothelial growth factor-B by VEGFR-1(D2): recognition and specificity. J. Biol. Chem. · 2010
- Vascular endothelial growth factor receptor-1 in human cancer: concise review and rationale for development of IMC-18F1 (Human antibody targeting vascular endothelial growth factor receptor-1). Cancer · 2010
- Structure-function analysis of VEGF receptor activation and the role of coreceptors in angiogenic signaling. Biochim. Biophys. Acta · 2010
- VEGFs and receptors involved in angiogenesis versus lymphangiogenesis. Curr. Opin. Cell Biol. · 2009
- VEGF receptor protein-tyrosine kinases: structure and regulation. Biochem. Biophys. Res. Commun. · 2008
- … and 31 more in the literature graph