ArticleMolecular and cellular biology1998
Mutations in the extracellular domain cause RET loss of function by a dominant negative mechanism.
Article in Molecular and cellular biology, 1998. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
19 citing papers in PubMed, 1 synthesis or guideline pooled it, 58 citations in OpenAlex.
- MtDNA meta-analysis reveals both phenotype specificity and allele heterogeneity: a model for differential association.Scientific reports · 2017Pooled it
- A Single RET Mutation in Hirschsprung Disease Induces Intestinal Aganglionosis Via a Dominant-Negative Mechanism.Cellular and molecular gastroenterology and hepatology · 2023Article
- TheAIMS neuroscience · 2022Review
- RET receptor signaling: Function in development, metabolic disease, and cancer.Proceedings of the Japan Academy. Series B, Physical and biological sciences · 2022Review
- Roles of theJMA journal · 2020Review
- Demonstration of a potent RET transcriptional inhibitor for the treatment of medullary thyroid carcinoma based on an ellipticine derivative.International journal of oncology · 2017Article
- SRY interference of normal regulation of the RET gene suggests a potential role of the Y-chromosome gene in sexual dimorphism in Hirschsprung disease.Human molecular genetics · 2015Article
- Structure and physiology of the RET receptor tyrosine kinase.Cold Spring Harbor perspectives in biology · 2013Review
- Alternative splicing results in RET isoforms with distinct trafficking properties.Molecular biology of the cell · 2012Article
- Predominant RET Germline Mutations in Exons 10, 11, and 16 in Iranian Patients with Hereditary Medullary Thyroid Carcinoma.Journal of thyroid research · 2011Article
- Mammal-restricted elements predispose human RET to folding impairment by HSCR mutations.Nature structural & molecular biology · 2010Article
- Renal aplasia in humans is associated with RET mutations.American journal of human genetics · 2008Article
- Article
- Exon 5 of the RET proto-oncogene: a newly detected risk exon for familial medullary thyroid carcinoma, a novel germ-line mutation Gly321Arg.Journal of endocrinological investigation · 2005Article
- Novel germline mutation in the transmembrane region of RET gene close to Cys634Ser mutation associated with MEN 2A syndrome.Journal of molecular medicine (Berlin, Germany) · 2005Article
- A targeting mutation of tyrosine 1062 in Ret causes a marked decrease of enteric neurons and renal hypoplasia.Molecular and cellular biology · 2004Article
- Gene therapeutic approaches for medullary thyroid carcinoma treatment.Journal of molecular medicine (Berlin, Germany) · 2003Review
- Association of RET protooncogene codon 45 polymorphism with Hirschsprung disease.American journal of human genetics · 1999Article
- An impaired routing of wild-type aquaporin-2 after tetramerization with an aquaporin-2 mutant explains dominant nephrogenic diabetes insipidus.The EMBO journal · 1999Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The RET proto-oncogene encodes a tyrosine kinase receptor expressed in neuroectoderm-derived cells. Mutations in specific regions of the gene are responsible for the tumor syndromes multiple endocrine neoplasia types 2A and 2B (MEN 2A and 2B), while mutations along the entire gene are involved in a developmental disorder of the gastrointestinal tract, Hirschsprung's disease (HSCR disease). Two mutants in the extracellular domain of RET, one associated with HSCR disease and one carrying a flag epitope, were analyzed to investigate the impact of the mutations on RET function. Both mutants were impeded in their maturation, resulting in the lack of the 170-kDa mature form and the accumulation of the 150-kDa immature form in the endoplasmic reticulum. Although not exposed on the cell surface, the 150-kDa species formed dimers and aggregates; this was more pronounced in a double mutant bearing a MEN 2A mutation. Tyrosine phosphorylation and the transactivation potential were drastically reduced in single and double mutants. Finally, in cotransfection experiments both mutants exerted a dominant negative effect over protoRET and RET2A through the formation of a heteromeric complex that prevents their maturation and function. These results suggest that HSCR mutations in the extracellular region cause RET loss of function through a dominant negative mechanism.
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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.