The guanylate cyclase/receptor family of proteins.
Guanylate cyclase, which catalyzes the formation of cGMP from GTP, exists in both the soluble and particulate fractions of cells. At least two different cellular compartments for the particulate enzyme exist: the plasma membrane and cytoskeleton. The enzyme form found in the soluble fraction is a heterodimer that can be regulated by free radicals and nitrovasodilators, whereas the membrane form exists as a single-chain polypeptide that can be regulated by various peptides. These peptides include resact and speract obtained from eggs and atrial natriuretic peptides (ANP). The species of guanylate cyclase present in cytoskeletal fractions resists solubilization with non-ionic detergents; its structural properties are not yet known. cDNAs encoding the membrane form of guanylate cyclase have been isolated from different tissues and species, and in all cases the DNA sequences predict a protein containing a single transmembrane domain. The carboxyl (intracellular) domain is highly conserved from sea urchins through mammals, whereas the extracellular domain (amino terminus) varies considerably. The predicted amino acid sequences demonstrate that the membrane form of guanylate cyclase is a member of a diverse and complex family of proteins that includes a low molecular weight ANP receptor, protein kinases, and the cytoplasmic form of guanylate cyclase. cDNA encoding a membrane form of the enzyme from mammalian tissues has been expressed in cultured cells, and the expressed guanylate cyclase specifically binds ANP and is activated by ANP. The membrane form of guanylate cyclase, then, serves as a cell surface receptor, representing the first recognized protein to directly catalyze formation of a low molecular weight second messenger in response to ligand binding.
Schulz
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Howard Hughes Medical Institute, Vanderbilt University School of Medicine, Nashville, Tennessee 37232-0295.
Chinkers
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Garbers
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D000595:Amino Acid Sequence; D000818:Animals; D002462:Cell Membrane / Q000502:physiology / Q000648:ultrastructure; D004247:DNA / Q000235:genetics; D006162:Guanylate Cyclase / Q000502:physiology*; D008969:Molecular Sequence Data; D005810:Multigene Family; D051381:Rats; D011956:Receptors, Cell Surface / Q000502:physiology*; D012617:Sea Urchins
D011956:Receptors, Cell Surface; D004247:DNA; D006162:Guanylate Cyclase