Phosphorylation of high‐ and low‐molecular‐mass atrial natriuretic peptide analogs by cyclic AMP‐dependent protein kinase

Abstract

Synthetic high- and low-molecular-mass atrial peptides were phosphorylated in vitro by cyclic AMP-dependent protein kinase and [32P]ATP. From a series of atrial peptide analogs, it was deduced that the amino acid sequence, Arg101Ser104 of atriopeptin was required for optimal phosphorylation. Phosphorylated AP(99–126) was less potent than the parent atriopeptin in vasorelaxant activity and receptor-binding properties. These results indicate that the presence of a phosphate group at the N-terminus of AP(99–126) decreases the interaction of the peptide with its receptor and, as a consequence, decreases bioactivity. These observations are in contrast to those of Rittenhouse et al. [(1986) J. Biol. Chem. 261, 7607–7610] who reported that phosphorylation of AP(101–126) enhanced the stimulation of Na/K/Cl cotransport in cultured vascular smooth muscle cells