Phosphorylation of high- and low-molecular-mass atrial natriuretic peptide analogs by cyclic AMP-dependent protein kinase.
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.
Olins
G M
GM
Searle Research and Development, Chesterfield, MO 63198.
Mehta
P P
PP
Blehm
D J
DJ
Patton
D R
DR
Zupec
M E
ME
Whipple
D E
DE
Tjoeng
F S
FS
Adams
S P
SP
Olins
P O
PO
Gierse
J K
JK
D000818:Animals; D009320:Atrial Natriuretic Factor / Q000031:analogs & derivatives* / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism; D066298:In Vitro Techniques; D008168:Lung; D008970:Molecular Weight; D010766:Phosphorylation; D011494:Protein Kinases / Q000378:metabolism*; D011817:Rabbits; D017461:Receptors, Atrial Natriuretic Factor; D011956:Receptors, Cell Surface / Q000378:metabolism; D013329:Structure-Activity Relationship; D013438:Sulfhydryl Compounds / Q000378:metabolism
D011956:Receptors, Cell Surface; D013438:Sulfhydryl Compounds; D009320:Atrial Natriuretic Factor; D000242:Cyclic AMP; D011494:Protein Kinases; D017461:Receptors, Atrial Natriuretic Factor