title: ATP modulation of the ligand binding and signal transduction activities of the type C natriuretic peptide receptor guanylate cyclase.
abstract: The type C natriuretic peptide (CNP)-activated guanylate cyclase (CNP-RGC) is a single-chain transmembrane-spanning protein, containing both CNP binding and catalytic cyclase activities. Upon binding CNP to the extracellular receptor domain, the cytosolic catalytic domain of CNP-RGC is activated, generating the second messenger cyclic GMP. Obligatory in this activation process is an intervening signal transduction step which is regulated by ATP binding to the cyclase. This bridges the events of ligand binding and cyclase activation. A defined sequence motif (Gly499-Xa-Xa-Xa-Gly503), termed ATP regulatory module (ARM), is critical for this step. The present study shows that ATP not only amplifies the signal transduction step, it also concomitantly reduces the ligand binding activity of CNP-RGC. Reduction in the ligand binding activity is a consequence of the transformation of the high affinity receptor-form to the low affinity receptor-form. A single ARM residue Gly499 is critical in the mediation of both ATP effects, signal transduction and ligand binding activity of the receptor. Thus, this residue represents an ATP bimodal switch to turn the CNP signal on and off.
authors: Unit of Regulatory and Molecular Biology, Pennsylvania College of Optometry, Philadelphia 19141, USA.
authors: T
authors: T
authors: Duda
authors: R K
authors: RK
authors: Sharma
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D002461:Cell Line, Transformed; D002522:Chlorocebus aethiops; D006162:Guanylate Cyclase / Q000378:metabolism*; D008024:Ligands; D020098:Natriuretic Peptide, C-Type; D011506:Proteins; D015398:Signal Transduction / Q000502:physiology*
chemical_list: D008024:Ligands; D011506:Proteins; D020098:Natriuretic Peptide, C-Type; D000255:Adenosine Triphosphate; D006162:Guanylate Cyclase