The primary structure of a plasma membrane guanylate cyclase demonstrates diversity within this new receptor family.
Atrial natriuretic peptide (ANP) binds directly to a plasma membrane form of guanylate cyclase (GC-A), stimulating the production of the second messenger cyclic GMP. We show that a second guanylate cyclase/receptor (GC-B) exists, with distinctly different specificities for various natriuretic peptides. A cDNA clone encoding GC-B was isolated by low-stringency screening of a rat brain cDNA library using GC-A cDNA as a probe. The deduced amino acid sequence of GC-B is 78% identical with GC-A within the intracellular region, but 43% identical within the extracellular domain. Cyclic GMP concentrations in cells transfected with GC-A were half-maximally elevated at 3 nM ANP, 25 nM brain natriuretic peptide (BNP), and 65 nM atriopeptin 1, while 25 microM ANP, 6 microM BNP, and greater than 100 microM atriopeptin 1 were required for half-maximal stimulation of GC-B. The potencies of natriuretic peptides on GC-A and GC-B activity are therefore markedly different; furthermore, despite the specificity of GC-B for BNP, the relatively high BNP concentration required to elicit a response suggests the possible presence of a more potent, unidentified natural ligand.
Schulz
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Howard Hughes Medical Institute, Vanderbilt University Medical Center, Nashville, Tennessee 37232.
Singh
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Bellet
R A
RA
Singh
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G
Tubb
D J
DJ
Chin
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H
Garbers
D L
DL
D000595:Amino Acid Sequence; D000818:Animals; D009320:Atrial Natriuretic Factor / Q000378:metabolism; D001483:Base Sequence; D001921:Brain / Q000201:enzymology; D002460:Cell Line; D002462:Cell Membrane / Q000201:enzymology; D003001:Cloning, Molecular; D004247:DNA / Q000235:genetics; D005796:Genes; D014644:Genetic Variation; D006162:Guanylate Cyclase / Q000235:genetics*; D008969:Molecular Sequence Data; D005810:Multigene Family; D009693:Nucleic Acid Hybridization; D051381:Rats; D017461:Receptors, Atrial Natriuretic Factor; D011956:Receptors, Cell Surface / Q000235:genetics*; D012689:Sequence Homology, Nucleic Acid; D014162:Transfection
D011956:Receptors, Cell Surface; D009320:Atrial Natriuretic Factor; D004247:DNA; D006162:Guanylate Cyclase; D017461:Receptors, Atrial Natriuretic Factor