Find VEGFA Products Interaction Network for VEGFA VEGFA Details

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Synonyms: Gd-vegf, MGC70609, VEGF, Vegf-3, VEGF-E, VEGF1, VEGF120, Vegf164, Vegf165, Vegf188, VEGFA, Vegfa 188, VPF, VPF/VEGF

VEGF Pathway

The vascular endothelial growth factor (VEGF) family is composed of several isotypes, including VEGF (VEGF-A, vascular permeability factor), VEGF-B, VEGF-C and VEGF-D which exist as numerous splice variant isoforms. VEGF is a heparin-binding, disulfide-linked dimer glycoprotein that exists in various secreted isoforms, VEGF121, VEGF145 and VEGF165 and a membrane bound VEGF189. It shares significant homology with PDGF-A and PDGF-B. VEGF-B splice variants include a soluble VEGF-B167 form and a cell surface associated VEGF-B186 form. VEGF is able to heterodimerize with other forms of VEGF. It can form a heterodimer with VEGF-B, or non-VEGF factors such as placenta growth factor (PlGF). The existence of multiple VEGF isotypes and isoforms and their ability to heterodimerize provides for sophisticated tissue-specific regulation of cellular processes.

Members of the VEGF family promote two very important processes in vivo, angiogenesis and lymphangiogenesis, which involve growth of new blood and lymphatic vessels from pre-existing vasculature, respectively. These processes control the normal processes of wound healing, ovarian-follicular development, endometrium growth and pathological processes such as retinopathies, rheumatoid arthritis and solid tumor growth. Lymphangiogenesis is correlated with lymph node metastasis and cancer spread via the lymphatic system.

VEGF-A and VEGF-B promote vascular angiogenesis primarily through activation of vascular endothelial cell associated VEGFR-1 (Flt1) and VEGFR-2 (Flk1/KDR). On the other hand, VEGF-C and VEGF-D which are ligands for VEGFR-2 and VEGFR-3 promote angiogenesis and lymphangiogenesis. VEGFR-2 is considered to be a major mediator of angiogenesis and VEGFR-3 (FLT4), which is localized on lymphatic endothelial cells, has emerged as a primary mediator of lymphangiogenesis. These receptors are tyrosine kinases that are linked to cell survival, proliferation, and motility processes via phospholipase C (PLC)/calcium and PKC; PI3-K/AKT; and the RAS/RAF/MEK/ERK pathways.