FLT1

GeneName

FLT1

Summary

FLT1, also known as VEGFR-1, is a 151 kDa transmembrane receptor that plays a pivotal role in angiogenesis and vascular development. It is expressed in various tissues, including endothelial cells and monocytes, and is localised to the plasma membrane and extracellular space. FLT1 functions primarily as a receptor for vascular endothelial growth factor (VEGF) and placental growth factor (PlGF), mediating cell surface receptor protein tyrosine kinase signalling. It is involved in processes such as blood vessel morphogenesis, cell migration, and the regulation of endothelial cell proliferation, contributing to the dynamic regulation of vascular networks.

Importance

FLT1 is relevant to: - Angiogenesis and vascular development, making it a target for therapies in cancer and other diseases characterised by abnormal blood vessel growth. - The regulation of immune responses through its role in monocyte chemotaxis and interaction with immune cells. - Understanding placental development and related disorders due to its function as a placental growth factor receptor. - Potential therapeutic interventions in conditions like diabetic retinopathy and age-related macular degeneration, where VEGF signalling is implicated.

Top Products

For researchers investigating FLT1, we highly recommend the top-selling recombinant antibody, Anti-VEGF Receptor 1 antibody [Y103] (ab32152). This well-cited antibody has garnered 379 citations, underscoring its reliability and trust within the scientific community. It has been validated for use in several applications, including Western blotting (WB), immunohistochemistry (IHC), and immunoprecipitation (IP), making it a versatile tool for your research needs. The recombinant nature of this antibody ensures batch-to-batch consistency, providing confidence in your experimental results. The Recombinant Human VEGF Receptor 1 protein (Active) ELISA Kit (ab281824) is an excellent option for researchers looking to study FLT1 in their experiments.

Abcam Product Citation Summary

The data indicates a significant focus on the FLT1 target across various species, particularly in studies related to angiogenesis, diabetes, and cancer. The use of multiple applications, primarily Western blotting and immunohistochemistry, highlights the importance of FLT1 in understanding vascular biology and its implications in disease contexts such as cancer and ischemia.

Abcam Product Citation Table

Domain

The second and third Ig-like C2-type (immunoglobulin-like) domains are sufficient for VEGFA binding.

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 (PubMed:16685275).

Isoform 1

Phosphorylates PLCG.

Isoform 2

May function as decoy receptor for VEGFA.

Isoform 3

May function as decoy receptor for VEGFA.

Isoform 4

May function as decoy receptor for VEGFA.

Isoform 7

Has a truncated kinase domain; it increases phosphorylation of SRC at 'Tyr-418' by unknown means and promotes tumor cell invasion.

Involvement in disease

Can contribute to cancer cell survival, proliferation, migration, and invasion, and tumor angiogenesis and metastasis. May contribute to cancer pathogenesis by promoting inflammatory responses and recruitment of tumor-infiltrating macrophages.

Abnormally high expression of soluble isoforms (isoform 2, isoform 3 or isoform 4) may be a cause of preeclampsia.

Post-translational modifications

N-glycosylated.

Ubiquitinated after VEGFA-mediated autophosphorylation, leading to proteolytic degradation.

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-1169 is important for interaction with PLCG. Phosphorylation at Tyr-1213 is important for interaction with PIK3R1, PTPN11, GRB2, and PLCG. Phosphorylation at Tyr-1333 is important for endocytosis and for interaction with CBL, NCK1 and CRK. Is probably dephosphorylated by PTPRB.

Sequence Similarities

Belongs to the protein kinase superfamily. Tyr protein kinase family. CSF-1/PDGF receptor subfamily.

Tissue Specificity

Detected in normal lung, but also in placenta, liver, kidney, heart and brain tissues. Specifically expressed in most of the vascular endothelial cells, and also expressed in peripheral blood monocytes. Isoform 2 is strongly expressed in placenta. Isoform 3 is expressed in corneal epithelial cells (at protein level). Isoform 3 is expressed in vascular smooth muscle cells (VSMC).

Cellular localization

• Isoform 1
• Cell membrane
• Single-pass type I membrane protein
• Endosome
• Autophosphorylation promotes ubiquitination and endocytosis.
• Isoform 2
• Secreted
• Isoform 3
• Secreted
• Isoform 4
• Secreted
• Isoform 5
• Cytoplasm
• Isoform 6
• Cytoplasm
• Isoform 7
• Cytoplasm

Alternative names

FLT, FRT, VEGFR1, FLT1, Vascular endothelial growth factor receptor 1, VEGFR-1, Fms-like tyrosine kinase 1, Tyrosine-protein kinase FRT, Tyrosine-protein kinase receptor FLT, Vascular permeability factor receptor, FLT-1

Database links

swissprot:P17948 omim:165070 entrezGene:2321

Other research areas

• Cardiovascular
• Immuno-oncology
• Immunology & Infectious Disease
• Neuroscience