Core sequence of ATP regulatory module in receptor guanylate cyclases.
Atrial natriuretic factor (ANF) and C-type natriuretic peptide (CNP)-activated guanylate cyclases are single-chain transmembrane-spanning proteins, containing both ligand binding and catalytic activities. In both proteins, ligand binding to the extracellular receptor domain activates the cytosolic catalytic domain, generating the second messenger cyclic GMP. Studies with ANF receptor guanylate cyclase (ANF-RGC) have indicated that obligatory in this activation process is an ATP-dependent step. ATP directly binds to the cyclase and bridges the events of ligand binding and signal transduction. A defined ATP-regulated module (ARM) sequence (Gly503-Arg-Gly-Ser-Asn-Tyr-Gly509) in the cyclase is critical in the ATP-mediated event. Through genetic remodeling techniques, we have now identified the core ARM sequence that is essential in both ANF and CNP signaling. This sequence is Gly-Xa-Xa-Xa-Gly, represented by Gly505-Ser-Asn-Tyr-Gly509 in the case of ANF-RGC ARM and by Gly499-Ser-Ser-Tyr-Gly503 in the CNP receptor guanylate cyclase ARM.
Duda
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Unit of Regulatory and Molecular Biology, Pennsylvania College of Optometry, Philadelphia 19141.
Goraczniak
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RM
Sharma
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D000255:Adenosine Triphosphate / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002462:Cell Membrane / Q000378:metabolism; D002522:Chlorocebus aethiops; D006162:Guanylate Cyclase / Q000378:metabolism*; D066298:In Vitro Techniques; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D009838:Oligodeoxyribonucleotides / Q000737:chemistry; D017461:Receptors, Atrial Natriuretic Factor / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000378:metabolism*; D013329:Structure-Activity Relationship
D009838:Oligodeoxyribonucleotides; D011956:Receptors, Cell Surface; D000255:Adenosine Triphosphate; D006162:Guanylate Cyclase; D017461:Receptors, Atrial Natriuretic Factor; C073616:atrial natriuretic factor receptor C