ArticleThe Journal of biological chemistry2014
Functional rescue of Kallmann syndrome-associated prokineticin receptor 2 (PKR2) mutants deficient in trafficking.
Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 22 citations in OpenAlex.
- Genetic Polymorphisms of Prokineticins and Prokineticin Receptors Associated with Human Disease.Life (Basel, Switzerland) · 2024Review
- Therapeutic Potential of Targeting Prokineticin Receptors in Diseases.Pharmacological reviews · 2023Review
- A functional spectrum of PROKR2 mutations identified in isolated hypogonadotropic hypogonadism.Human molecular genetics · 2023Article
- Phenotypic and genotypic landscape of PROKR2 in neuroendocrine disorders.Frontiers in endocrinology · 2023Review
- Trafficking-defective mutant PROKR2 cycles between endoplasmic reticulum and Golgi to attenuate endoplasmic reticulum stress.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Prokineticin-Receptor Network: Mechanisms of Regulation.Life (Basel, Switzerland) · 2022Review
- Targeting trafficking as a therapeutic avenue for misfolded GPCRs leading to endocrine diseases.Frontiers in endocrinology · 2022Review
- Misfolded G Protein-Coupled Receptors and Endocrine Disease. Molecular Mechanisms and Therapeutic Prospects.International journal of molecular sciences · 2021Review
- Modeling mutant/wild-type interactions to ascertain pathogenicity of PROKR2 missense variants in patients with isolated GnRH deficiency.Human molecular genetics · 2018Article
- A Novel Drug-Mouse Phenotypic Similarity Method Detects Molecular Determinants of Drug Effects.PLoS computational biology · 2016Article
- Study on KAL1 Gene Mutations in Idiopathic Hypogonadotropic Hypogonadism Patients with X-Linked Recessive Inheritance.International journal of molecular and cellular medicine · 2015Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Mutations in the G protein-coupled prokineticin receptor 2 (PKR2) are known to cause Kallmann syndrome and idiopathic hypogonadotropic hypogonadism manifesting with delayed puberty and infertility. Some of the mutant receptors are not routed to the cell surface; instead, they are trapped in the cellular secretory pathway. The cell-permeant agonists/antagonists have been used to rescue some membrane receptors that are not targeted onto the cell membrane. Here, we chose three disease-associated mutations (W178S, G234D, and P290S), which all resulted in retention of PKR2 intracellularly. We show that a small molecule PKR2 antagonist (A457) dramatically increased cell surface expression and rescued the function of P290S PKR2, but had no effect on W178S and G234D PKR2. Furthermore, we also tested chemical chaperone glycerol on the cell surface expression and function of PKR2 mutants. Treatment with 10% glycerol significantly increased the cell surface expression and signaling of P290S and W178S PKR2. These data demonstrate that some Kallmann syndrome-associated, intracellularly retained mutant PKR2 receptors can be functionally rescued, suggesting a potential treatment strategy for patients bearing such mutations.
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