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VEGFR3 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'. Interacts with VEGFC and VEGFD. Monomer in the absence of bound VEGFC or VEGFD. Homodimer in the presence of bound VEGFC or VEGFD. Can also form a heterodimer with KDR. Interacts with PTPN14; the interaction is enhanced by stimulation with VEGFC. Interacts with CRK, GRB2, PTK2/FAK1, SHC1, PIK3R1 and PTPN11/SHP- 2. Identified in a complex with SRC and ITGB1. Detected in endothelial cells. Widely expressed. Detected in fetal spleen, lung and brain. Detected in adult liver, muscle, thymus, placenta, lung, testis, ovary, prostate, heart, and kidney. 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. Belongs to the protein kinase superfamily. Tyr protein kinase family. CSF-1/PDGF receptor subfamily. 3 isoforms of the human protein are produced by alternative splicing. Note: This description may include information from UniProtKB.
Protein type: EC; Kinase, protein; Membrane protein, integral; Protein kinase, TK; Protein kinase, tyrosine (receptor); TK group; VEGFR family
Chromosomal Location of Human Ortholog: 5q35.3
Cellular Component: plasma membrane; receptor complex
Molecular Function: growth factor binding; protein binding; protein phosphatase binding; transmembrane receptor protein tyrosine kinase activity; vascular endothelial growth factor receptor activity
Biological Process: blood vessel morphogenesis; lymph vessel development; lymphangiogenesis; negative regulation of apoptosis; peptidyl-tyrosine phosphorylation; positive regulation of cell proliferation; positive regulation of endothelial cell proliferation; positive regulation of JNK cascade; positive regulation of MAPKKK cascade; positive regulation of protein amino acid phosphorylation; protein amino acid autophosphorylation; sprouting angiogenesis; transmembrane receptor protein tyrosine kinase signaling pathway; vascular endothelial growth factor receptor signaling pathway; vasculature development
Disease: Hemangioma, Capillary Infantile; Lymphedema, Hereditary, Ia
Reference #:  P35916 (UniProtKB)
Alt. Names/Synonyms: FLT-4; FLT4; FLT41; Fms-like tyrosine kinase 4; fms-related tyrosine kinase 4; LMPH1A; PCL; soluble VEGFR3 variant 1; soluble VEGFR3 variant 2; soluble VEGFR3 variant 3; Tyrosine-protein kinase receptor FLT4; Vascular endothelial growth factor receptor 3; VEGFR-3; VEGFR3; VGFR3
Gene Symbols: FLT4
Molecular weight: 152,757 Da
Basal Isoelectric point: 5.9  Predict pI for various phosphorylation states
CST Pathways:  Tyrosine Kinases & Substrates
Protein-Specific Antibodies or siRNAs from Cell Signaling Technology® Total Proteins
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