Post-translational processing of preprotachykinins. Isolation of protachykinin-(1-37)-peptide from human adrenal-medullary phaeochromocytoma tissue

The biosynthetic precursors of the mammalian tachykinins, α-, β- and γ-preprotachykinins, contain a common N-terminal region of 74 amino acids. A polyclonal antiserum was raised against a synthetic peptide representing N-tyrosylated β-preprotachykinin-(48-56)-peptide as predicted from the nucleotide sequence of cloned DNA complementary to human β-preprotachykinin mRNA. By using this antiserum in radioimmunoassay, a single immunoreactive peptide was identified in an extract of a human pheochromocytoma that produced substance P and neurokinin A. Partial microsequencing and determination of the amino acid composition of the peptide indicated identity with preprotachykinin-(20-56)-peptide. Thus the data demonstrate that the Ala¹⁹-Glu²⁰ bond in preprotachykinin is the site of cleavage of the signal peptide.