THE SHORTEST ISOFORM OF HUMAN VASCULAR ENDOTHELIAL GROWTH-FACTOR VASCULAR-PERMEABILITY FACTOR (VEGF/VPF121) PRODUCED BY SACCHAROMYCES-CEREVISIAE PROMOTES BOTH ANGIOGENESIS AND VASCULAR-PERMEABILITY

Vascular endothelial growth factor/vascular permeability factor (VEGF/VPF) is a multifunctional cytokine that is expressed as four isoforms having 206, 189, 165, and 121 amino acids in humans. We constructed a system that produces the shortest isoform of human VEGF/VPF in Saccharomyces cerevisiae (yVEGF/VPF121). Active yVEGF/VPF121 was secreted from the yeast cells as a glycosylated dimeric protein. Various biological activities of the purified yVEGF/VPF121 were examined. It bound to cell surface receptor(s) and stimulated the growth of human umbilical vein endothelial cells in culture at a dose similar to that of native VEGF/VPF. Purified yVEGF/VPF121 also induced angiogenesis in mice, and promoted the extravasation of plasma proteins from the blood vessels. These observations demonstrated that the shortest isoform of VEGF/VPF with an amino acid sequence of 121 residues contains enough information necessary to trigger both angiogenesis and the induction of vascular permeability upon binding to its cognate receptor(s).