The Carboxyl-terminal Domain(111–165) of Vascular Endothelial Growth Factor Is Critical for Its Mitogenic Potency

The VEGF angiogenic switch of fibroblasts is regulated by MMP-7 from cancer cells

“…Our data suggest a regulation of VEGF activity by CTGF and MMP-7 in human cells and tissues. Human MMP-7 and other MMPs do not cleave the predominant isoform of VEGF (VEGF 165 ) in vitro (Keyt et al, 1996;Hashimoto et al, 2002), which leads to selective degradation of CTGF and the release of VEGF activity . In contrast, MMP-7 and other MMPs modulate bioactivity of the corresponding isoform of mouse VEGF through intramolecular cleavage (Lee et al, 2005).…”

1H, 13C, and 15N backbone assignment and secondary structure of the receptor‐binding domain of vascular endothelial growth factor

“…Preliminary homonuclear TOCSY spectra (7, = 30 ms) of the receptor-binding domain of VEGF obtained by plasmin cleavage of VEGF16s (VEGF""') (Keyt et al, 1996a), acquired at 40°C pH 6.5, in general showed only weak correlations between the amide and alpha protons. For a few residues, however, strong side chain-to-amide proton correlations were observed (data not shown).…”

“…With the exception of VEGFIzl, the different isoforms are highly basic and bind tightly to extracellular heparin or heparan sulfate-containing proteoglycans Park et al, 1993). VEGF165 is the isoform expressed most abundantly, and can be cleaved by plasmin to yield a 1 10-residue fragment, VEGF"'" (Keyt et al, 1996a). Proteolytic removal of the heparin-binding C-terminal domain has no effect on the ability of VEGF to bind KDR, but is associated with a significant loss in bioactivity, suggesting that the heparin-binding domain of VEGF165 is required to sequester it to the extracellular matrix (Keyt et al, 1996a).…”

“…VEGF165 is the isoform expressed most abundantly, and can be cleaved by plasmin to yield a 1 10-residue fragment, VEGF"'" (Keyt et al, 1996a). Proteolytic removal of the heparin-binding C-terminal domain has no effect on the ability of VEGF to bind KDR, but is associated with a significant loss in bioactivity, suggesting that the heparin-binding domain of VEGF165 is required to sequester it to the extracellular matrix (Keyt et al, 1996a). Limited sequence homology suggests that the receptor-binding domain (VEGF'" l o ) is a member of the PDGF subfamily of the cystine-knot growth factor superfamily of proteins and, as such, is expected to dimerize in an antiparallel side-by-side fashion (Sun & Davies, 1995).…”

Newly identified biologically active and proteolysis-resistant VEGF-A isoform VEGF111 is induced by genotoxic agents

“…The amino acid sequence encoded by exon 5 includes the main site of cleavage by plasmin (Claffey et al, 1995;Keyt et al, 1996) and matrix metalloproteinases (Lee et al, 2005). Exon 6 encodes the sequence that binds to heparin and a cell surface retention consensus sequence.…”