scholarly journals Heterozygous Mutations in Natriuretic Peptide Receptor-B (NPR2) Are Associated with Short Stature

2006 ◽  
Vol 91 (4) ◽  
pp. 1229-1232 ◽  
Author(s):  
Robert C. Olney ◽  
Hülya Bükülmez ◽  
Cynthia F. Bartels ◽  
Timothy C. R. Prickett ◽  
Eric A. Espiner ◽  
...  
Keyword(s):  
Short Stature ◽  
Natriuretic Peptide ◽  
Natriuretic Peptide Receptor ◽  
Peptide Receptor

scholarly journals Heterozygous Mutations in Natriuretic Peptide Receptor-B (NPR2) Gene as a Cause of Short Stature in Patients Initially Classified as Idiopathic Short Stature

2013 ◽  
Vol 98 (10) ◽  
pp. E1636-E1644 ◽  
Author(s):  
Gabriela A. Vasques ◽  
Naoko Amano ◽  
Ana J. Docko ◽  
Mariana F. A. Funari ◽  
Elisangela P. S. Quedas ◽  
...  
Keyword(s):  
Short Stature ◽  
Natriuretic Peptide ◽  
Idiopathic Short Stature ◽  
Natriuretic Peptide Receptor ◽  
Peptide Receptor

scholarly journals Intact Kinase Homology Domain of Natriuretic Peptide Receptor-B Is Essential for Skeletal Development

2007 ◽  
Vol 92 (10) ◽  
pp. 4009-4014 ◽  
Author(s):  
Rumi Hachiya ◽  
Yuko Ohashi ◽  
Yasutomi Kamei ◽  
Takayoshi Suganami ◽  
Hiroshi Mochizuki ◽  
...  
Keyword(s):  
Short Stature ◽  
Natriuretic Peptide ◽  
Functional Significance ◽  
Skeletal Development ◽  
Natriuretic Peptide Receptor ◽  
Wild Type ◽  
Peptide Receptor ◽  
Cgmp Production ◽  
Kinase Homology Domain ◽  
Kinase Homology

Abstract Context: Natriuretic peptide receptor-B (NPR-B, GC-B in rodents; gene name NPR2) is a guanylyl cyclase-coupled receptor that mediates the effect of C-type natriuretic peptide. Homozygous mutations in human NPR-B cause acromesomelic dysplasia, type Maroteaux (OMIM 602875), an autosomal recessive skeletal dysplasia. NPR-B has an intracellular kinase homology domain (KHD), which has no kinase activity, and its functional significance in vivo is currently unknown. Objective: We examined the functional significance of a novel NPR-B KHD mutation in humans. Patients and Methods: A 28-yr-old Japanese male presented with marked short stature (118.5 cm, −9.3 sd). His limbs showed marked shortening in the middle and distal segments. His parents had relatively short stature with height z-scores of −2.75 and −0.98 (his father and mother, respectively). Direct sequencing of coding region of the NPR2 gene of the family was performed. The mutant receptor activity was investigated by saturation binding assay and cGMP measurement. Additionally, interaction between the mutant and wild type allele was investigated by the titration experiments. Results: We identified a novel missense mutation L658F in KHD of NPR-B in homozygous and heterozygous states in the patient and his parents, respectively. The mutation conferred normal binding affinity for C-type natriuretic peptide but no discernible ligand-induced cGMP production. Furthermore, L658F mutant impaired wild-type NPR-B-mediated cGMP production in a dose-dependent manner, suggesting that short stature found in L658F heterozygote can be caused by its dominant-negative effect. Conclusions: This study provides the first evidence that intact KHD of NPR-B is essential for skeletal development.

scholarly journals Heterozygous Mutations in Natriuretic Peptide Receptor-B (NPR2) Gene as a Cause of Short Stature

2015 ◽  
Vol 36 (4) ◽  
pp. 474-481 ◽  
Author(s):  
Sophie R. Wang ◽  
Christina M. Jacobsen ◽  
Heather Carmichael ◽  
Aaron B. Edmund ◽  
Jerid W. Robinson ◽  
...  
Keyword(s):  
Short Stature ◽  
Natriuretic Peptide ◽  
Natriuretic Peptide Receptor ◽  
Peptide Receptor

Role of Natriuretic Peptide Receptor Type C in Dahl Salt-Sensitive Hypertensive Rats

Hypertension ◽  
1997 ◽  
Vol 30 (2) ◽  
pp. 177-183 ◽  
Author(s):  
Miki Nagase ◽  
Katsuyuki Ando ◽  
Takeshi Katafuchi ◽  
Akira Kato ◽  
Shigehisa Hirose ◽  
...  
Keyword(s):  
Natriuretic Peptide ◽  
Receptor Type ◽  
Natriuretic Peptide Receptor ◽  
Hypertensive Rats ◽  
Peptide Receptor ◽  
Type C

Allotopic antagonism of the non-peptide atrial natriuretic peptide (ANP) antagonist HS-142-1 on natriuretic peptide receptor NPR-A

2002 ◽  
Vol 362 (2) ◽  
pp. 231-237 ◽  
Author(s):  
Hugo POIRIER ◽  
Jean LABRECQUE ◽  
Julie DESCHÊNES ◽  
André DeLÉAN
Keyword(s):  
Atrial Natriuretic Peptide ◽  
Natriuretic Peptide ◽  
Mode Of Action ◽  
Transmembrane Domain ◽  
Peptide Binding ◽  
Natriuretic Peptide Receptor ◽  
Receptor Dimerization ◽  
Peptide Receptor ◽  
Peptide Binding Site ◽  
Atrial Natriuretic

The microbial polysaccharide HS-142-1 has been documented as an antagonist of natriuretic peptides. It inhibits activation and peptide binding to both guanylate receptors natriuretic peptide receptor (NPR)-A and NPR-B, but has no effect on the non-cyclase receptor NPR-C. At first sight the effect of HS-142-1 on peptide binding appears to be surmountable, suggesting that it might be competitive despite its chemically divergent nature. We explored its mode of action on wild-type NPR-A (WT), on a disulphide-bridged constitutively active mutant (C423S) and on truncated mutants lacking either their cytoplasmic domain (ΔKC) or both the cytoplasmic and the transmembrane domains (ECD). On the WT, HS-142-1 inhibited atrial natriuretic peptide (ANP) binding with a pK value of 6.51±0.07 (Kd = 0.31μM). It displayed a similar effect on the C423S mutant (pK = 6.31±0.11), indicating that its action might not be due to interference with receptor dimerization. HS-142-1 also inhibited ANP binding to ΔKC with a pK of 7.05±0.05 (Kd = 0.089μM), but it was inactive on ANP binding to ECD at a concentration of 10−4M, suggesting that the antagonism was not competitive at the peptide-binding site located on the ECD and that the transmembrane domain might be required. HS-142-1 also enhanced dissociation of NPR-A-bound 125I-ANP in the presence of excess unlabelled ANP, implying an allotopic (allosteric) mode of action for the antagonist.

scholarly journals Structure of the bovine atrial natriuretic peptide receptor (type C) gene

1991 ◽  
Vol 266 (17) ◽  
pp. 11122-11125
Author(s):  
T. Saheki ◽  
T. Mizuno ◽  
T. Iwata ◽  
Y. Saito ◽  
T. Nagasawa ◽  
...  
Keyword(s):  
Atrial Natriuretic Peptide ◽  
Natriuretic Peptide ◽  
Receptor Type ◽  
Natriuretic Peptide Receptor ◽  
Peptide Receptor ◽  
Type C ◽  
Atrial Natriuretic Peptide Receptor ◽  
Atrial Natriuretic
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