Biosynthesis of phosphorylated forms of corticotropin-related peptides.

Phosphorylated forms of corticotropin[ACTH (1-39)], corticotropin-like intermediary lobe peptide[CLIP, ACTH (18-39)], and the common precursor for ACTH and beta-lipotropin (beta-LPH) have been identified in extracts of rat pituitaries, 32P-Labeled inorganic phosphate was successfully incorporated into ACTH (1-39), CLIP, and the ACTH/beta-LPH precursor in rat neurointermediary lobe explants and into ACTH (1-39) in isolated rat anterior pituitary cells. After peptidase digestion of the labeled CLIP and ACTH, the radioactive phosphate was recoverable as O-phosphoserine. The serine residue at position 31 was the only amino acid found to be phosphorylated in CLIP and ACTH (1-39). The unphosphorylated forms of both peptides were also synthesized. The demonstration of he incorporation of [32P]phosphate into CLIP, ACTH (1-39), and the ACTH/beta-LPH precursor is consistent with the hypothesis that, within the rat intermediary lobe, phosphorylated CLIP is derived from a phosphorylated form of the common precursor, with phosphorylated ACTH (1-39) acting as a biosynthetic intermediate.