Human atrial natriuretic peptide receptor defines a new paradigm for second messenger signal transduction.
We isolated cDNAs encoding a 115 kd human atrial natriuretic peptide (alpha ANP) receptor (ANP-A receptor) that possesses guanylate cyclase activity, by low-stringency hybridization with sea urchin Arbacia punctulata membrane guanylate cyclase probes. The human ANP-A receptor has a 32 residue signal sequence followed by a 441 residue extracellular domain homologous to the 60 kd ANP-C receptor. A 21 residue transmembrane domain precedes a 568 residue cytoplasmic domain with homology to the protein kinase family and to a subunit of the soluble guanylate cyclase. COS-7 cells transfected with an ANP-A receptor expression vector displayed specific [125I]alpha ANP binding, and exhibited alpha ANP stimulated cGMP production. These data demonstrate a new paradigm of cellular signal transduction where extracellular ligand binding allosterically regulates cyclic nucleotide second-messenger production by a receptor cytoplasmic catalytic domain.
Lowe
D G
DG
Department of Molecular Biology, Genentech, Inc., South San Francisco, CA 94080.
Chang
M S
MS
Hellmiss
R
R
Chen
E
E
Singh
S
S
Garbers
D L
DL
Goeddel
D V
DV
D000595:Amino Acid Sequence; D000818:Animals; D009320:Atrial Natriuretic Factor / Q000378:metabolism*; D001483:Base Sequence; D004247:DNA / Q000235:genetics; D006162:Guanylate Cyclase / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000378:metabolism; D017461:Receptors, Atrial Natriuretic Factor; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism*; D012617:Sea Urchins; D015290:Second Messenger Systems; D012689:Sequence Homology, Nucleic Acid
D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D009320:Atrial Natriuretic Factor; D004247:DNA; D006162:Guanylate Cyclase; D017461:Receptors, Atrial Natriuretic Factor