VEGF Mechanism

By Dr. Ananya Mandal, MDReviewed by Sally Robertson, B.Sc.

VEGF or vascular endothelial growth factor is a signalling protein made by cells that stimulates the formation of new blood vessels. There are several different classes of VEGF that play different roles in the body, both in normal bodily process and pathological processes.

VEGF proteins form a particular sub-family of growth factors referred to as the platelet-derived growth factor family of cystine-knot growth factors. They are key signalling proteins involved in two different types of blood vessel formation, namely vasculogenesis and angiogenesis. Vasculogenesis refers to the de novo formation of vessels during development of the embryo’s circulatory system, while angiogenesis describes the formation of blood vessels from vasculature that already exists.

VEGF is made by various different types of cells including macrophages, keratinocytes, tumor cells, platelets, and mesangial cells in the kidney. As well as promoting the formation of blood and lymph vessels, VEGF plays a role in the formation of bones and blood, as well as being required for wound healing and embryonic development.

VEGF proteins promote cellular responses when they bind to tyrosine kinase receptors or VEGF receptors. These VEGF receptors lie on the cell surface and when VEGF binds to them, they undergo dimerization and transphosphorylation to become activated. This activation process occurs at various different sites, at different times and to different extents. The VEGF receptor is made up of an extracellular portion comprising 7 immunoglobulin-like domains, a transmembrane spanning portion and an intracellular portion that contains a split tyrosine-kinase domain.

One of the most important members of the VEGF family, VEGF-A, binds to the receptors - VEGFR-1 and VEGFR-2. VEGFR-2 is thought to mediate most of the cellular responses to VEGF. The function of VEGFR-1, however, is less clear, but this receptor seems to modulate VEGFR-2 signalling. VEGFR-1 also acts as a dummy/decoy receptor that can sequester the VEGF from VEGFR-2 binding. This process is important when blood vessels are developing in the embryo. VEGF-C and VEGF-D can bind exclusively to a third receptor, VEGFR-3, which mediates the formation of lymphatic capillaries.

Further Reading

• All VEGF Content
• What is VEGF?
• VEGF Classification
• VEGF Production
• VEGF Clinical Significance