Hormonal induction of low affinity receptor guanylyl cyclase.
We describe a unique transient binding phenomenon for atrial natriuretic peptide (ANP) binding to the natriuretic peptide receptor-A (NPR-A) guanylyl cyclase stably expressed in 293 cells. The time course of ANP binding to intact cells peaked at 15 min followed by a subsequent decrease. Reduced binding was a consequence of an ANP induced low affinity state of NPR-A, and required the receptors' kinase homology domain. In a particulate fraction, ANP-stimulated cGMP production was dependent on ATP as a cofactor, and ATP promoted a lower affinity state. Our findings suggest that the kinase homology domain of NPR-A mediates the regulatory action of ATP, not only for signal transduction, but in the modulation of NPR-A hormone affinity.
Jewett
J R
JR
Department of Molecular Biology, Genentech, Inc., South San Francisco, CA 94080.
Koller
K J
KJ
Goeddel
D V
DV
Lowe
D G
DG
D000255:Adenosine Triphosphate / Q000378:metabolism; D000584:Amiloride / Q000494:pharmacology; D009320:Atrial Natriuretic Factor / Q000378:metabolism*; D002478:Cells, Cultured; D003001:Cloning, Molecular; D004790:Enzyme Induction; D006162:Guanylate Cyclase / Q000096:biosynthesis*; D006801:Humans; D008954:Models, Biological; D010770:Phosphotransferases / Q000378:metabolism; D011485:Protein Binding / Q000187:drug effects; D017461:Receptors, Atrial Natriuretic Factor / Q000378:metabolism*; D015398:Signal Transduction; D013379:Substrate Specificity
D000584:Amiloride; D009320:Atrial Natriuretic Factor; D000255:Adenosine Triphosphate; D010770:Phosphotransferases; D006162:Guanylate Cyclase; D017461:Receptors, Atrial Natriuretic Factor