title: Single amino acid residue-linked signaling shifts in the transduction activities of atrial and type C natriuretic factor receptor guanylate cyclases.
abstract: The type A (ANF) and the type C (CNP) natriuretic factor-activated guanylate cyclases, respectively termed as ANF-RGC and CNP-RGC, are single-chain transmembrane-spanning proteins, containing ligand binding and catalytic cyclase domains at two opposite ends of the protein. The binding activity resides at the N-terminal extracellular region and the catalytic cyclase activity at the carboxyl end. The ANF-RGC residue Leu-364, residing in the extracellular region, is critical for the ANF-binding activity; the CNP-RGC residue Glu-332 is critical for the CNP-binding activity. The counter part of CNP-RGC-Glu-332 residue is the ANF-RGC residue Gln-338 and of ANF-RGC-Leu-364 residue in CNP-RGC is the Valine-358. The present study shows a remarkable signal switching phenomenon associated with these residues. By changing the ANF-RGC residue Gln-338 to Glu, ANF-RGC switches from no to significant CNP signal transduction activity; similarly, a change from Valine-358 to Leu generates ANF signal transduction activity in CNP-RGC. These acquired signal transduction activities in the cyclases are in addition to their natural signal transduction activities. Thus, these new cyclases show both ANF and CNP signaling activities.
authors.affiliation: Unit of Regulatory and Molecular Biology, Pennsylvania College of Optometry, Philadelphia 19141, USA.
authors.forename: T
authors.initials: T
authors.lastname: Duda
authors.forename: R M
authors.initials: RM
authors.lastname: Goraczniak
authors.forename: R K
authors.initials: RK
authors.lastname: Sharma
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites / Q000235:genetics; D002460:Cell Line; D006162:Guanylate Cyclase / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D016297:Mutagenesis, Site-Directed; D017461:Receptors, Atrial Natriuretic Factor / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D014162:Transfection
chemical_list: D006162:Guanylate Cyclase; D017461:Receptors, Atrial Natriuretic Factor; C073616:atrial natriuretic factor receptor C