Primary structure and functional expression of the human receptor for Escherichia coli heat-stable enterotoxin.
Heat-stable enterotoxin (STa) produced by Escherichia coli induces intestinal secretion in mammals by binding to the brush border membrane of the small intestine and activating guanylyl cyclase. We report here the cloning and expression of a cDNA encoding the human receptor for STa. The receptor contains both an extracellular ligand binding site and a cytoplasmic guanylyl cyclase catalytic domain, making it a member of the same receptor family as the natriuretic peptide receptors. Stable mammalian cell lines over-expressing the STa receptor specifically bind 125I-STa (Kd approximately 1.0 nM) and respond to STa by dramatically increasing (approximately 50-fold) cellular cGMP levels. Sequence comparisons between the human and the rat STa receptors show less conservation in the extracellular domain than similar comparisons of natriuretic peptide receptors. This divergence may indicate important species differences in ligand-receptor interaction.
Department of Molecular Biology, Genentech, Inc., South San Francisco, California 94080.
F J
FJ
de Sauvage
T R
TR
Camerato
D V
DV
Goeddel
D000595:Amino Acid Sequence; D009320:Atrial Natriuretic Factor / Q000378:metabolism; D001427:Bacterial Toxins / Q000235:genetics* / Q000378:metabolism; D001483:Base Sequence; D001665:Binding Sites; D002384:Catalysis; D004247:DNA / Q000235:genetics; D004768:Enterotoxins / Q000235:genetics* / Q000378:metabolism; D004789:Enzyme Activation; D029968:Escherichia coli Proteins; D015870:Gene Expression; D006162:Guanylate Cyclase / Q000378:metabolism; D006801:Humans; D007421:Intestine, Small / Q000378:metabolism; D008871:Microvilli / Q000378:metabolism; D008969:Molecular Sequence Data; D012689:Sequence Homology, Nucleic Acid
D001427:Bacterial Toxins; D004768:Enterotoxins; D029968:Escherichia coli Proteins; C034151:heat stable toxin (E coli); D009320:Atrial Natriuretic Factor; D004247:DNA; D006162:Guanylate Cyclase