FLT4 - Vascular endothelial growth factor receptor 3 - human protein (Function)
 
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FLT4 »  Vascular endothelial growth factor receptor 3   [ EC 2.7.10.1 ]  (VEGFR-3)
 
Protein also known as:  Tyrosine-protein kinase receptor FLT4.
Gene name:  FLT4
Entry whose protein(s) existence is based on evidence at protein level
extend overview
1 179 3
GENE REF ISO

Function

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Overview 
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'.  
15
  • CuratedUniProtKB
GO molecular function 
ATP bindingdefinition[GO:0005524]  
  • IEAUniProtKB KW
Growth factor bindingdefinition[GO:0019838]  
1
  • IPIUniProtKB
Protein bindingdefinition[GO:0005515]  
4
  • IPIIntAct
Protein phosphatase bindingdefinition[GO:0019903]  
1
  • IPIUniProtKB
Transmembrane receptor protein tyrosine kinase activitydefinition[GO:0004714]  
1
  • IMPUniProtKB
Vascular endothelial growth factor-activated receptor activitydefinition[GO:0005021]  
3
  • IMPUniProtKB
  • IDAMGI
GO biological process 
Blood vessel morphogenesisdefinition[GO:0048514]  
  • ISSOrtholog Curator
Cellular response to vascular endothelial growth factor stimulusdefinition[GO:0035924]  
2
  • IMPUniProtKB
Lymph vessel developmentdefinition[GO:0001945]  
  • ISSOrtholog Curator
Lymphangiogenesisdefinition[GO:0001946]  
1
  • IMPUniProtKB
  • ISSOrtholog Curator
Negative regulation of apoptotic processdefinition[GO:0043066]  
1
  • IMPUniProtKB
Peptidyl-tyrosine phosphorylationdefinition[GO:0018108]  
1
  • IDAUniProtKB
Positive regulation of cell proliferationdefinition[GO:0008284]  
3
  • IMPUniProtKB
  • IGIMGI
Positive regulation of endothelial cell migrationdefinition[GO:0010595]  
1
  • IMPUniProtKB
Positive regulation of endothelial cell proliferationdefinition[GO:0001938]  
1
  • IMPUniProtKB
Positive regulation of ERK1 and ERK2 cascadedefinition[GO:0070374]  
1
  • IMPUniProtKB
Positive regulation of JNK cascadedefinition[GO:0046330]  
1
  • IMPUniProtKB
Positive regulation of MAPK cascadedefinition[GO:0043410]  
1
  • IMPUniProtKB
Positive regulation of protein kinase C signalingdefinition[GO:0090037]  
1
  • IMPUniProtKB
Positive regulation of protein phosphorylationdefinition[GO:0001934]  
2
  • IMPUniProtKB
Positive regulation vascular endothelial growth factor productiondefinition[GO:0010575]  
1
  • IMPUniProtKB
Protein autophosphorylationdefinition[GO:0046777]  
2
  • IDAUniProtKB
Regulation of blood vessel remodelingdefinition[GO:0060312]  
  • ISSOrtholog Curator
Sprouting angiogenesisdefinition[GO:0002040]  
  • ISSOrtholog Curator
Transmembrane receptor protein tyrosine kinase signaling pathwaydefinition[GO:0007169]  
1
  • TASPINC
Vascular endothelial growth factor receptor signaling pathwaydefinition[GO:0048010]  
4
  • IMPUniProtKB
  • IGIMGI
Vasculature developmentdefinition[GO:0001944]  
  • ISSOrtholog Curator
Enzymatic activity 
This protein acts as an enzyme. It is known to catalyze the following reaction
EC 2.7.10.1: ATP + a [protein]-L-tyrosine ADP + a [protein]-L-tyrosine phosphate.  
2
  • CuratedUniProtKB
It is regulated in the following manner
Present in an inactive conformation in the absence of bound ligand. Binding of VEGFC or VEGFD leads to dimerization and activation by autophosphorylation on tyrosine residues. Inhibited by MAZ51.  
3
  • CuratedUniProtKB
 
More information is available from:
Pathways 
According to KEGG, this protein belongs to the following pathways:
Cytokine-cytokine receptor interaction  hsa04060+2324  
Focal adhesion  hsa04510+2324  
According to Reactome, this protein belongs to the following pathway:
Signal Transduction  REACT_111102  
 

Keywords

Biological process 
Angiogenesis  definition   [KW-0037]
Molecular function 
Kinase  definition   [KW-0418]
Receptor  definition   [KW-0675]
Transferase  definition   [KW-0808]
Tyrosine-protein kinase  definition   [KW-0829]
Technical term 
Reference proteome  definition   [KW-1185]
 

Further external links

Other
GeneWiki: FLT4
GenomeRNAi: 2324
PRO: PR:P35916
Chemistry
GuidetoPHARMACOLOGY: 1814