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. 1989 May;8(5):1377–1384. doi: 10.1002/j.1460-2075.1989.tb03518.x

Human atrial natriuretic peptide receptor defines a new paradigm for second messenger signal transduction.

D G Lowe 1, M S Chang 1, R Hellmiss 1, E Chen 1, S Singh 1, D L Garbers 1, D V Goeddel 1
PMCID: PMC400964  PMID: 2569967

Abstract

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.

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