ReviewIUBMB life2020
Emerging roles of the αC-β4 loop in protein kinase structure, function, evolution, and disease.
Review in IUBMB life, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
What it found
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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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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
19 citing papers in PubMed, 45 citations in OpenAlex.
- RAF inhibitors activate the integrated stress response by direct activation of GCN2.Nature communications · 2025Article
- A structure-based tool to interpret the significance of kinase mutations in clinical next generation sequencing in cancer.Frontiers in oncology · 2025Article
- CEP192 localises mitotic Aurora-A activity by priming its interaction with TPX2.The EMBO journal · 2024Article
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- Article
- Conserved regulatory motifs in the juxtamembrane domain and kinase N-lobe revealed through deep mutational scanning of the MET receptor tyrosine kinase domain.bioRxiv : the preprint server for biology · 2024Article
- Structural dynamics of RAF1-HSP90-CDC37 and HSP90 complexes reveal asymmetric client interactions and key structural elements.Communications biology · 2024Article
- Survivin Mediates Mitotic Onset in HeLa Cells Through Activation of the Cdk1-Cdc25B Axis.Research square · 2024Article
- Beyond Amyloid: A Machine Learning-Driven Approach Reveals Properties of Potent GSK-3β Inhibitors Targeting Neurofibrillary Tangles.International journal of molecular sciences · 2024Article
- An update on evolutionary, structural, and functional studies of receptor-like kinases in plants.Frontiers in plant science · 2024Review
- A point mutation in the kinase domain of CRK10 leads to xylem vessel collapse and activation of defence responses in Arabidopsis.Journal of experimental botany · 2023Article
- Tree visualizations of protein sequence embedding space enable improved functional clustering of diverse protein superfamilies.Briefings in bioinformatics · 2023Article
- Saturation mutagenesis of a predicted ancestral Syk-family kinase.Protein science : a publication of the Protein Society · 2022Article
- Divergent kinase WNG1 is regulated by phosphorylation of an atypical activation sub-domain.The Biochemical journal · 2022Article
- The Role of Hsp90 in Retinal Proteostasis and Disease.Biomolecules · 2022Review
- The mechanism of Raf activation through dimerization.Chemical science · 2021Article
- Conformation and dynamics of the kinase domain drive subcellular location and activation of LRRK2.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Active and Inactive Cdc42 Differ in Their Insert Region Conformational Dynamics.Biophysical journal · 2021Article
- Kinase Function of Brassinosteroid Receptor Specified by Two Allosterically Regulated Subdomains.Frontiers in plant science · 2021Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
The faithful propagation of cellular signals in most organisms relies on the coordinated functions of a large family of protein kinases that share a conserved catalytic domain. The catalytic domain is a dynamic scaffold that undergoes large conformational changes upon activation. Most of these conformational changes, such as movement of the regulatory αC-helix from an "out" to "in" conformation, hinge on a conserved, but understudied, loop termed the αC-β4 loop, which mediates conserved interactions to tether flexible structural elements to the kinase core. We previously showed that the αC-β4 loop is a unique feature of eukaryotic protein kinases. Here, we review the emerging roles of this loop in kinase structure, function, regulation, and diseases. Through a kinome-wide analysis, we define the boundaries of the loop for the first time and show that sequence and structural variation in the loop correlate with conformational and regulatory variation. Many recurrent disease mutations map to the αC-β4 loop and contribute to drug resistance and abnormal kinase activation by relieving key auto-inhibitory interactions associated with αC-helix and inter-lobe movement. The αC-β4 loop is a hotspot for post-translational modifications, protein-protein interaction, and Hsp90 mediated folding. Our kinome-wide analysis provides insights for hypothesis-driven characterization of understudied kinases and the development of allosteric protein kinase inhibitors.
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What OpenQuestion holds
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.