vascular endothelial growth factor C; VEGF-C; vascular endothelial growth factor-related protein; VRP; Flt4 ligand; Flt4-L (VEGFC)

Function

• growth factor active in angiogenesis, & endothelial cell growth
• stimulates endothelial cell proliferation & migration
• has effects on the permeability of blood vessels
• may function in angiogenesis of the venous & lymphatic vascular systems during embryogenesis, & in the maintenance of differentiated lymphatic endothelium in adults
• binds & activates VEGFR-2 receptor (Flk1) & VEGFR-3 receptor (Flt4)
• macrophage secretion of VEGF-C is stimulated by NFAT5 (TonEBP) that is produced in response to hypertonic conditions
• undergoes a complex proteolytic maturation which generates a variety of processed secreted forms with increased activity toward VEGFR-3, but only the fully processed activates VEGFR-2
• forms an antiparallel homodimer linked by disulfide bonds
• before secretion, a cleavage occurs between Arg-227 & Ser-228 producing an heterotetramer
• the next extracellular step of the processing removes the N-terminal propeptide
• finally the mature VEGF-C is composed mostly of two VEGF homology domains (VHDs) bound by non-covalent interactions

Structure

• homodimer; non-covalent & antiparallel
• belongs to the PDGF/VEGF growth factor family

Compartment

secreted

Expression

• spleen, lymph node, thymus, appendix, bone marrow, heart, placenta, ovary, skeletal muscle, prostate, testis, colon & small intestine & fetal liver, lung & kidney, but not in peripheral blood lymphocyte

Pathology

• defects in macrophage NFAT5-stimulated VEGF-C secretion may play a role in salt-sensitive hypertension

More general terms

• vascular endothelial growth factor family protein (VEGF family)

Database

• UniProt: http://www.uniprot.org/uniprot/P49767.html
• Entrez gene: http://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=Retrieve&dopt=Graphics&list_uids=7424
• Kegg: http://www.genome.jp/dbget-bin/www_bget?hsa:7424
• OMIM: https://mirror.omim.org/entry/601528