Thymidine phosphorylase activity of platelet‐derived endothelial cell growth factor is responsible for endothelial cell mitogenicity

Recombinant human platelet‐derived endothelial cell growth factor, expressed in the yeast Saccharomyces cerevisiae was purified to greater than 98% purity by anion‐exchange and hydroxyapatite chromatography. It was shown to possess theymidine phosphorolytic activity in vitro (pH optiomum, pH 5.3; Km, 0.11 mM; Vmax, 12.5 mmol min−1 mg −1; turnover number, 9.4 s−1). Covalent modification simultaneously inhibited the enzymatic and mitogenic properties of the protein, while interaction with a cell‐surface receptor was not required to stimulate mitogenesis. Purified Escherichia coli thymidine phosphorylase was also mitogenic toward endothelial cells. It is proposed that platelet‐derived endothelial cell growth factor is human thymidine phosphorylase which promotes endothelial cell proliferation by reducing thymidine levels that would otherwise be inhibitory to endotheial cell growth.