Pre - proparathyroid hormone identified by cell - free translation of messenger RNA from hyperplastic human...

An 8-15S fraction of RNA isolated from hyperplastic human parathyroid tissue (primary chief-cell hyperplasia) and translated in a cell-free extract of wheat germ directs the synthesis of a protein that shares antigenic determinants and tryptic peptides with parathyroid hormone and its previously recognized immediated precursor, proparathyroid hormone. In addition, the protein contains tryptic peptides not found in proparathyroid hormone and migrates more slowly than does proparathyroid hormone on both urea-acid and urea-sodium dodecyl sulfate polyacrylamide gels, indicating that it is more acidic and larger than proparathyroid hormone. Sequential Edman degradation of the cell-free protein, radiolabeled with [35S]methionine, for 25 cycles released [35S]methionine at cycles 1, 7, 11, and 14, indicating that the NH2-terminal peptide sequence of the protein differs from that of both proparathyroid hormone and parathyroid hormone. We propose that this protein is an early biosynthetic precursor of human parathyroid hormone, pre-proparathyroid hormone, analogous to that identified recently by in vitro translation of bovine parathyroid mRNA.