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

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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@article{Lowe1989HumanAN, title={Human atrial natriuretic peptide receptor defines a new paradigm for second messenger signal transduction.}, author={David Lowe and Mun Seock Chang and R Hellmiss and Ellson Chen and S K Singh and David L. Garbers and David V. Goeddel}, journal={The EMBO journal}, year={1989}, volume={8 5}, pages={1377-84} }