VEGF receptor

VEGF receptor
File:1djs.jpg fms-related tyrosine kinase 1 (vascular endothelial growth factor/vascular permeability factor receptor)
Identifiers
Symbol	VEGF
InterPro	IPR009135
Membranome	1335

Identifiers
Symbol	FLT1
Alt. symbols	FLT
NCBI gene	2321
HGNC	3763
OMIM	165070
RefSeq	NM_002019
UniProt	P17948
Other data
EC number	2.7.1.112
Locus	Chr. 13 q12
Search for Structures Swiss-model Domains InterPro

kinase insert domain receptor (a type III receptor tyrosine kinase)
Identifiers
Symbol	KDR
Alt. symbols	FLK1, VEGFR, VEGFR2, CD309
NCBI gene	3791
HGNC	6307
OMIM	191306
RefSeq	NM_002253
UniProt	P35968
Other data
EC number	2.7.1.112
Locus	Chr. 4 q11-q12
Search for Structures Swiss-model Domains InterPro

fms-related tyrosine kinase 4
Identifiers
Symbol	FLT4
Alt. symbols	VEGFR3, PCL
NCBI gene	2324
HGNC	3767
OMIM	136352
RefSeq	NM_002020
UniProt	P35916
Other data
EC number	2.7.1.112
Locus	Chr. 5 q34-q35
Search for Structures Swiss-model Domains InterPro

VEGF receptors (VEGFRs) are receptors for vascular endothelial growth factor (VEGF). There are three main subtypes of VEGFR, numbered 1, 2 and 3. Depending on alternative splicing, they may be membrane-bound (mbVEGFR) or soluble (sVEGFR).

Inhibitors of VEGFR are used in the treatment of cancer.

VEGF

Main article: Vascular endothelial growth factor

Vascular endothelial growth factor (VEGF) is an important signaling protein involved in both vasculogenesis (the formation of the circulatory system) and angiogenesis (the growth of blood vessels from pre-existing vasculature). As its name implies, VEGF activity is restricted mainly to cells of the vascular endothelium, although it does have effects on a limited number of other cell types (e.g. stimulation monocyte/macrophage migration). In vitro, VEGF has been shown to stimulate endothelial cell mitogenesis and cell migration. VEGF also enhances microvascular permeability and is sometimes referred to as vascular permeability factor.

Receptor biology

File:VEGF receptors.png

Ligands for different VEGF receptors.

All members of the VEGF family stimulate cellular responses by binding to tyrosine kinase receptors (the VEGFRs) on the cell surface, causing them to dimerize and become activated through transphosphorylation. The VEGF receptors have an extracellular portion consisting of 7 immunoglobulin-like domains, a single transmembrane spanning region and an intracellular portion containing a split tyrosine-kinase domain.

VEGF-A binds to VEGFR-1 (Flt-1) and VEGFR-2 (KDR/Flk-1). VEGFR-2 appears to mediate almost all of the known cellular responses to VEGF. The function of VEGFR-1 is less well defined, although it is thought to modulate VEGFR-2 signaling. Another function of VEGFR-1 is to act as a dummy/decoy receptor, sequestering VEGF from VEGFR-2 binding (this appears to be particularly important during vasculogenesis in the embryo). In fact, an alternatively spliced form of VEGFR-1 (sFlt1) is not a membrane bound protein but is secreted and functions primarily as a decoy. A third receptor has been discovered (VEGFR-3), however, VEGF-A is not a ligand for this receptor. VEGFR-3 mediates lymphangiogenesis in response to VEGF-C and VEGF-D.

In addition to binding to VEGFRs, VEGF binds to receptor complexes consisting of both neuropilins and VEGFRs. This receptor complex has increased VEGF signalling activity in endothelial cells (blood vessels). Neuropilins (NRP) are pleiotropic receptors and therefore other molecules may interfere with the signalling of the NRP/VEGFR receptor complexes. For example, Class 3 semaphorins compete with VEGF₁₆₅ for NRP binding and could therefore regulate VEGF-mediated angiogenesis.

External links

• VEGF+Receptors at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
• Proteopedia Vascular_Endothelial_Growth_Factor_Receptor - the Vascular Endothelial Growth Factor Receptor Structure in Interactive 3D