Mammalian cell proteins, modified post-translationally by derivatives of [3H]mevalonic acid, were subjected to methylation and sulfonium salt cleavage reactions previously used to release isoprenoids from cysteine residues in yeast peptides. The labeled isoprenoid extracted into chloroform comigrated with farnesol through a series of chromatography steps including Sep-Pak C-18 fractionation, size exclusion on Bio-Beads, and reverse-phase chromatography. Further resolution of the material by normal phase liquid chromatography and thin layer chromatography demonstrated the presence of farnesol, nerolidol, and other unidentified hydrophobic derivatives. Similar products were generated when S-farnesyl cysteine was subjected to the methylation and cleavage procedures. These preliminary findings suggest that farnesylation of cysteine residues accounts for the well documented incorporation of mevalonic acid into mammalian cell proteins.
Animals Cell Line