The polypeptide P16 is a carboxy-terminal cleavage product of rat growth hormone in anterior pituitary and GH3 pituitary tumor cells.

P16 is a small polypeptide originally found in GH3 rat pituitary tumor cells whose expression is tightly linked to the expression of rat GH (rGH) at a genetic level. It is estimated to be 3-5 kilodaltons smaller than rGH and exhibits the same complex response to T3, dexamethasone, and insulin in GH3 cells as does rGH. P16 was also found in high but variable abundance in anterior but not posterior pituitary. To approach the question of whether it arises from a unique gene or derives instead from the rGH gene by a posttranscriptional mechanism, we have measured its structural relatedness to rGH by peptide mapping techniques. From partial peptide maps of rGH and P16 by V8 protease, it appeared that the two proteins were related by loss of a common, small peptide. Both proteins also contained many tryptic peptides in common. Cleavage by N-chlorosuccinimide at tryptophan residues showed that rGH and P16 both contained the same N-terminal peptide but differed in their C-termini. Hence, P16 differs from rGH by loss of an amino acid segment somewhere in the C-terminus. Charge calibration of two-dimensional gels indicated that P16 was more acidic than rGH by at least five negative charges. These observations taken together imply that rGH gives rise to P16 by a highly specific cleavage in the C-terminus mostly likely between residues 152 and 156. This region also harbors an alanine-leucine at which pro-rGH is cleaved to remove the 26 amino acid signal peptide.