ArticleThe Biochemical journal2012
Assessing the range of kinase autoinhibition mechanisms in the insulin receptor family.
Article in The Biochemical journal, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed, 87 citations in OpenAlex.
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- Autoinhibited Protein Database: a curated database of autoinhibitory domains and their autoinhibition mechanisms.Database : the journal of biological databases and curation · 2024Article
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- A review of complex hormone regulation in thyroid cancer: novel insights beyond the hypothalamus-pituitary-thyroid axis.Frontiers in endocrinology · 2024Review
- Looking lively: emerging principles of pseudokinase signaling.Trends in biochemical sciences · 2022Review
- Impact of metabolic syndrome on the risk of endometrial cancer and the role of lifestyle in prevention.Bosnian journal of basic medical sciences · 2022Review
- Activation of neurotrophin signalling with light‑inducible receptor tyrosine kinases.Molecular medicine reports · 2022Article
- Obesity and Thyroid Cancer Risk: An Update.International journal of environmental research and public health · 2022Review
- Dynamics of protein kinases and pseudokinases by HDX-MS.Methods in enzymology · 2022Article
- Evolution of Functional Diversity in the Holozoan Tyrosine Kinome.Molecular biology and evolution · 2021Article
- The intracellular domains of the EphB6 and EphA10 receptor tyrosine pseudokinases function as dynamic signalling hubs.The Biochemical journal · 2021Article
- Comparison of tyrosine kinase domain properties for the neurotrophin receptors TrkA and TrkB.The Biochemical journal · 2020Article
- Structural Insights into Pseudokinase Domains of Receptor Tyrosine Kinases.Molecular cell · 2020Article
- Structural basis of the transmembrane domain dimerization and rotation in the activation mechanism of the TRKA receptor by nerve growth factor.The Journal of biological chemistry · 2020Article
- Article
- Prospects for pharmacological targeting of pseudokinases.Nature reviews. Drug discovery · 2019Review
- What Makes a Kinase Promiscuous for Inhibitors?Cell chemical biology · 2019Article
- Precision medicine review: rare driver mutations and their biophysical classification.Biophysical reviews · 2019Review
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
To investigate the range of autoinhibitory mechanisms used by TKDs (tyrosine kinase domains) from the insulin receptor family of RTKs (receptor tyrosine kinases), we determined crystal structures of TKDs from TrkA (tropomyosin receptor kinase A, a nerve growth factor receptor) and Ror2 (receptor tyrosine kinase-like orphan receptor 2, an unconventional Wnt receptor). TrkA autoinhibition closely resembles that seen for the insulin receptor, relying on projection of an activation loop tyrosine residue into the substrate-binding site and occlusion of the ATP-binding site by the activation loop. Ror2 employs similar mechanisms, but the unusual replacement of the phenylalanine residue in its Asp-Phe-Gly motif with leucine necessitates occlusion of the ATP-binding site by other means. The unusual Asp-Leu-Gly motif in Ror2 is displaced compared with other inactive kinases, allowing the activation loop to interact directly with the TKD's αC helix, in another mode of autoinhibition that is characteristic of the other extreme of this receptor family: ALK (anaplastic lymphoma kinase) and Met. These findings provide insight into the expected range of activating mutations in these TKDs in cancer. We also describe symmetrical dimers of the inactive TrkA TKD resembling those found in other RTKs, possibly reflecting an arrangement of kinase domains in a pre-formed TrkA dimer.
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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.