ArticleBone2013
A human skeletal overgrowth mutation increases maximal velocity and blocks desensitization of guanylyl cyclase-B.
Article in Bone, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
What it found
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
12 citing papers in PubMed, 21 citations in OpenAlex.
- An Activating Deletion Variant in the Submembrane Region of Natriuretic Peptide Receptor-B Causes Tall Stature.The Journal of clinical endocrinology and metabolism · 2020Article
- Is C-type natriuretic peptide regulated by a feedback loop? A study on systemic and local autoregulatory effect.PloS one · 2020Article
- Exogenous C-type natriuretic peptide therapy for impaired skeletal growth in a murine model of glucocorticoid treatment.Scientific reports · 2019Article
- The pseudokinase domains of guanylyl cyclase-A and -B allosterically increase the affinity of their catalytic domains for substrate.Science signaling · 2019Article
- Regulation of the Natriuretic Peptide Receptor 2 (Npr2) by Phosphorylation of Juxtamembrane Serine and Threonine Residues Is Essential for Bifurcation of Sensory Axons.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2018Article
- Analysis of short-term treatment with the phosphodiesterase type 5 inhibitor tadalafil on long bone development in young rats.American journal of physiology. Endocrinology and metabolism · 2018Article
- Rats deficient C-type natriuretic peptide suffer from impaired skeletal growth without early death.PloS one · 2018Article
- Dephosphorylation is the mechanism of fibroblast growth factor inhibition of guanylyl cyclase-B.Cellular signalling · 2017Article
- Skeletal overgrowth-causing mutations mimic an allosterically activated conformation of guanylyl cyclase-B that is inhibited by 2,4,6,-trinitrophenyl ATP.The Journal of biological chemistry · 2017Article
- Catalytically Active Guanylyl Cyclase B Requires Endoplasmic Reticulum-mediated Glycosylation, and Mutations That Inhibit This Process Cause Dwarfism.The Journal of biological chemistry · 2016Article
- Heterozygous mutations in natriuretic peptide receptor-B (NPR2) gene as a cause of short stature.Human mutation · 2015Article
- Genes predict long distance migration and large body size in a migratory fish, Pacific lamprey.Evolutionary applications · 2014Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
Abstract
C-type natriuretic peptide (CNP) increases long bone growth by stimulating guanylyl cyclase (GC)-B/NPR-B/NPR2. Recently, a Val to Met missense mutation at position 883 in the catalytic domain of GC-B was identified in humans with increased blood cGMP levels that cause abnormally long bones. Here, we determined how this mutation activates GC-B. In the absence of CNP, cGMP levels in cells expressing V883M-GC-B were increased more than 20 fold compared to cells expressing wild-type (WT)-GC-B, and the addition of CNP only further increased cGMP levels 2-fold. In the absence of CNP, maximal enzymatic activity (Vmax) of V883M-GC-B was increased 15-fold compared to WT-GC-B but the affinity of the enzymes for substrate as revealed by the Michaelis constant (Km) was unaffected. Surprisingly, CNP decreased the Km of V883M-GC-B 10-fold in a concentration-dependent manner without increasing Vmax. Unlike the WT enzyme the Km reduction of V883M-GC-B did not require ATP. Unexpectedly, V883M-GC-B, but not WT-GC-B, failed to inactivate with time. Phosphorylation elevated but was not required for the activity increase associated with the mutation because the Val to Met substitution also activated a GC-B mutant lacking all known phosphorylation sites. We conclude that the V883M mutation increases maximal velocity in the absence of CNP, eliminates the requirement for ATP in the CNP-dependent Km reduction, and disrupts the normal inactivation process.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.