Vascular endothelial growth factor-A was originally isolated from tumor cells and referred to as Tumor Angiogenesis Factor. Although expressed at high levels in certain tumor-derived cells it is produced by a wide variety of cell types. In addition to stimulating vascular growth, vascular permeability, cell migration, and endothelial cell proliferation and growth, it may play a role in stimulating vasolidation via nitric oxide-dependent pathways and in inhibition of apoptosis. VEGF binds to the FLT1/VEGFR1 and KDR/VEGFR2 receptors, heparan sulfate and heparin. Alternative splicing of the mRNA for VEGF-A results in several isoforms of the protein being produced. Rat and bovine VEGF are one amino acid shorter than the human factor, and the bovine and human sequences show a homology of 95 percent. In contrast to other factors mitogenic for endothelial cells such as FGF-1, FGF-2 and PDGF, VEGF is synthesized as a precursor containing a typical hydrophobic secretory signal sequence of 26 amino acids. Glycosylation is not required for efficient secretion of VEGF. VEGF121 is acidic, freely secreted, and widely expressed. This isoform is produced by alternative promoter usage and alternative initiation. It starts at an alternative upstream CUG codon and is post-translationally processed to produce the secreted VEGF peptide and a N-terminal peptide N-VEGF. The unprocessed protein and the N-VEGF peptide may localize to the nucleus, the endoplasmic reticulum and the Golgi or the extracellular matrix. Recombinant Human VEGF-121 produced in E.coli is a double, non-glycosylated, polypeptide chain containing 121 amino acids and having a molecular mass of 28423 Daltons.