Molecular biology and biochemistry of the natriuretic peptide system. II: Natriuretic peptide receptors

K Nakao, Y Ogawa, S Suga, H Imura - Journal of hypertension, 1992 - journals.lww.com
K Nakao, Y Ogawa, S Suga, H Imura
Journal of hypertension, 1992journals.lww.com
Biologically active receptors Isolation and characterization of biologically active receptors
(particulate forms of guanylyl cyclase) have long been hampered by their low tissue contents
in mammals. In 1988, Singh et al.| 1] successfully isolated a complementary DNA (cDNA)
clone for the enzyme from sea urchin testis, which was subsequently used to isolate cDNA
clones for atrial natriuretic peptide (ANP). A and ANP-B receptors (Fig. 1)[2–5]. The rat
guanylyl-cyclase-A cDNA encodes a protein of 1057 amino acids containing a 28-amino …
Biologically active receptors Isolation and characterization of biologically active receptors (particulate forms of guanylyl cyclase) have long been hampered by their low tissue contents in mammals. In 1988, Singh et al.| 1] successfully isolated a complementary DNA (cDNA) clone for the enzyme from sea urchin testis, which was subsequently used to isolate cDNA clones for atrial natriuretic peptide (ANP). A and ANP-B receptors (Fig. 1)[2–5]. The rat guanylyl-cyclase-A cDNA encodes a protein of 1057 amino acids containing a 28-amino acid signal peptide [2], whilst the rat guanylyl cyclase-B cDNA encodes a protein of 1047 amino acids with a 22-amino acid signal peptide [5]. The expression of both receptor subtypes in cultured mammalian cells showed high guanylyl cyclase and natriuretic peptide binding activ-ities [2–5], despite different ligand selectivities. The cDNA sequences of both subtypes predicted a single transmembrane and three other functional domains (Fig 1). The extracellular domains of the rat guanylyl cyclase-A and guanylyl cyclase-B are 43% identical at the amino acid level, and approximately 30% identical to that of the clearance receptor (C receptor). This domain appears to be responsible for ligand binding. Just inside the plasma membrane lies a protein kinase-like domain, which is highly conserved between sea urchin and mammalian enzymes, and may func-tion as a nucleotide (adenosine triphosphate)-binding regulatory unit [6]. When this domain is deleted from the expressed rat guanylyl cyclase A, guanylyl cyclase is constitutively active, independent of ligand binding [7]. Near the carboxyl tail, there is a catalytic domain homologous with a soluble form of guanylyl cyclase
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