ArticleJournal of molecular biology2010
Identification of an allosteric signaling network within Tec family kinases.
Article in Journal of molecular biology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 42 citations in OpenAlex.
- Cryo-EM structure and biochemical characterization of a BRAF/CRAF heterodimer: Negative charge in the NtA motif is not required for RAF activation.bioRxiv : the preprint server for biology · 2026Article
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- Screening and Characterization of Allosteric Small Molecules Targeting Bruton's Tyrosine Kinase.Biochemistry · 2024Article
- PSNtools for standalone and web-based structure network analyses of conformational ensembles.Computational and structural biotechnology journal · 2022Article
- A mechanism for localized dynamics-driven activation in Bruton's tyrosine kinase.Royal Society open science · 2021Article
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- Reining in BTK: Interdomain Interactions and Their Importance in the Regulatory Control of BTK.Frontiers in cell and developmental biology · 2021Review
- webPSN v2.0: a webserver to infer fingerprints of structural communication in biomacromolecules.Nucleic acids research · 2020Article
- Lipid-targeting pleckstrin homology domain turns its autoinhibitory face toward the TEC kinases.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- Noncovalent inhibitors reveal BTK gatekeeper and auto-inhibitory residues that control its transforming activity.JCI insight · 2019Article
- Achieving a Graded Immune Response: BTK Adopts a Range of Active/Inactive Conformations Dictated by Multiple Interdomain Contacts.Structure (London, England : 1993) · 2017Article
- Functional validation reveals the novel missense V419L variant inCold Spring Harbor molecular case studies · 2017Article
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- Paralog-Specific Patterns of Structural Disorder and Phosphorylation in the Vertebrate SH3-SH2-Tyrosine Kinase Protein Family.Genome biology and evolution · 2016Article
- Protein Ensembles: How Does Nature Harness Thermodynamic Fluctuations for Life? The Diverse Functional Roles of Conformational Ensembles in the Cell.Chemical reviews · 2016Review
- Dynamic Allostery Mediated by a Conserved Tryptophan in the Tec Family Kinases.PLoS computational biology · 2016Article
- A dynamically coupled allosteric network underlies binding cooperativity in Src kinase.Nature communications · 2015Article
- A selective NMR probe to monitor the conformational transition from inactive to active kinase.ACS chemical biology · 2015Article
- Principles of allosteric interactions in cell signaling.Journal of the American Chemical Society · 2014Review
- A conserved isoleucine maintains the inactive state of Bruton's tyrosine kinase.Journal of molecular biology · 2014Article
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
The Tec family kinases are tyrosine kinases that function primarily in hematopoietic cells. The catalytic activity of the Tec kinases is positively influenced by the regulatory domains outside of the kinase domain. The current lack of a full-length Tec kinase structure leaves a void in our understanding of how these positive regulatory signals are transmitted to the kinase domain. Recently, a conserved structure within kinases, the 'regulatory spine', which assembles and disassembles as a kinase switches between its active and inactive states, has been identified. Here, we define the residues that comprise the regulatory spine within Tec kinases. Compared to previously characterized systems, the Tec kinases contain an extended regulatory spine that includes a conserved methionine within the C-helix and a conserved tryptophan within the Src homology 2-kinase linker of Tec kinases. This extended regulatory spine forms a conduit for transmitting the presence of the regulatory domains of Tec kinases to the catalytic domain. We further show that mutation of the gatekeeper residue at the edge of the regulatory spine stabilizes the regulatory spine, resulting in a constitutively active kinase domain. Importantly, the regulatory spine is preassembled in this gatekeeper mutant, rendering phosphorylation on the activation loop unnecessary for its activity. Moreover, we show that the disruption of the conserved electrostatic interaction between Bruton's tyrosine kinase R544 on the activation loop and Bruton's tyrosine kinase E445 on the C-helix also aids in the assembly of the regulatory spine. Thus, the extended regulatory spine is a key structure that is critical for maintaining the activity of Tec kinases.
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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.