ArticleCell reports2016
RET Functions as a Dual-Specificity Kinase that Requires Allosteric Inputs from Juxtamembrane Elements.
Article in Cell reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed.
- RET receptor tyrosine kinase architecture, assemblies, and activation.Endocrine-related cancer · 2026Review
- The oncogenic CCDC6-RET fusion protein is a dual ATP- and ADP-dependent kinase.Nature communications · 2026Article
- Variability in proliferative and migratory defects in Hirschsprung disease-associated RET pathogenic variants.American journal of human genetics · 2025Article
- The use of intuitive AF-based modelling for the understanding of activation and signalling through insulin-like receptors.Frontiers in endocrinology · 2025Review
- Variability in proliferative and migratory defects in Hirschsprung disease-associatedbioRxiv : the preprint server for biology · 2024Article
- CCDC6-RET fusion protein regulates Ras/MAPK signaling through the fusion- GRB2-SHC1 signal niche.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- RET signaling in breast cancer therapeutic resistance and metastasis.Breast cancer research : BCR · 2023Review
- Structural and dynamic determinants for highly selective RET kinase inhibition reveal cryptic druggability.Journal of advanced research · 2023Article
- Allosteric rescue of catalytically impaired ATP phosphoribosyltransferase variants links protein dynamics to active-site electrostatic preorganisation.Nature communications · 2022Article
- Bimodal regulation of axonal transport by the GDNF-RET signalling axis in healthy and diseased motor neurons.Cell death & disease · 2022Article
- Review
- The importance of the RET gene in thyroid cancer and therapeutic implications.Nature reviews. Endocrinology · 2021Review
- RET Receptor Tyrosine Kinase: Role in Neurodegeneration, Obesity, and Cancer.International journal of molecular sciences · 2020Review
- Two-step release of kinase autoinhibition in discoidin domain receptor 1.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- GGA3-mediated recycling of the RET receptor tyrosine kinase contributes to cell migration and invasion.Oncogene · 2020Article
- Tracing the origin and evolution of pseudokinases across the tree of life.Science signaling · 2019Article
- RET in breast cancer: pathogenic implications and mechanisms of drug resistance.Cancer drug resistance (Alhambra, Calif.) · 2019Review
- ATF4 destabilizes RET through nonclassical GRP78 inhibition to enhance chemosensitivity to bortezomib in human osteosarcoma.Theranostics · 2019Article
- Protein kinase D displays intrinsic Tyr autophosphorylation activity: insights into mechanism and regulation.FEBS letters · 2018Article
- Coupled regulation by the juxtamembrane and sterile α motif (SAM) linker is a hallmark of ephrin tyrosine kinase evolution.The Journal of biological chemistry · 2018Article
Corrections and comments
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Authors and funding
10 authors.
Funding
Abstract
Receptor tyrosine kinases exhibit a variety of activation mechanisms despite highly homologous catalytic domains. Such diversity arises through coupling of extracellular ligand-binding portions with highly variable intracellular sequences flanking the tyrosine kinase domain and specific patterns of autophosphorylation sites. Here, we show that the juxtamembrane (JM) segment enhances RET catalytic domain activity through Y687. This phospho-site is also required by the JM region to rescue an otherwise catalytically deficient RET activation-loop mutant lacking tyrosines. Structure-function analyses identified interactions between the JM hinge, αC helix, and an unconventional activation-loop serine phosphorylation site that engages the HRD motif and promotes phospho-tyrosine conformational accessibility and regulatory spine assembly. We demonstrate that this phospho-S909 arises from an intrinsic RET dual-specificity kinase activity and show that an equivalent serine is required for RET signaling in Drosophila. Our findings reveal dual-specificity and allosteric components for the mechanism of RET activation and signaling with direct implications for drug discovery.
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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.