Plasma membrane going around a banner with two different kinases and one affecting the nucleus/cell cycle. Phosphates are dotted in the background
Edited by
Volker Dötsch et al.

Special Issue: Allosteric Regulation of Kinase Activity

Our latest Special Issue brings together research on the allosteric regulation of kinase activity.
Collection
Vivid Biology. CC-BY4.0
  • Views 528

Phosphorylation plays a central role in all aspects of cellular biology. The complexity of the many similar enzymes within kinase families, often with different biological functions, has impacted our detailed understanding of signalling processes.

Breakthrough discoveries, however, have increased our understanding of the mechanisms that regulate kinase activity, and have shed light onto how activation of individual members of the same kinase family can trigger different signalling events.

To highlight these advances we are pleased to launch this Special Issue: Allosteric Regulation of Kinase Activity.

The articles in this Issue highlight how modern cellular, biochemical, biophysical and computational techniques are allowing deeper and more detailed studies of allosteric kinase regulation.

This Special Issue has been overseen by eLife Senior Editors Volker Dötsch, Goethe University, and Amy H Andreotti, Iowa State University, who take a look at the history of research in the area and the field today, and introduce the articles in the Special Issue in an editorial.

eLife introduced a new model of publishing in January 2023, and as a result this Special Issue includes research that has been through the traditional publishing process and Reviewed Preprints that have been through the new model.

Collection

    1. Biochemistry and Chemical Biology
    2. Structural Biology and Molecular Biophysics

    Special Issue: Allosteric regulation of kinase activity

    Amy H Andreotti, Volker Dötsch
    The articles in this special issue highlight how modern cellular, biochemical, biophysical and computational techniques are allowing deeper and more detailed studies of allosteric kinase regulation.
    Editorial
    Formats available:
    • HTML
    • PDF
    1. Biochemistry and Chemical Biology
    2. Structural Biology and Molecular Biophysics

    PH domain-mediated autoinhibition and oncogenic activation of Akt

    Hwan Bae, Thibault Viennet ... Philip A Cole
    Structural and biochemical analysis of semisynthetic Akt forms and mutants has revealed the importance of a key interaction network involving Arg86, Glu17, and Tyr18 that controls Akt conformation and activity.
    1. Biochemistry and Chemical Biology
    2. Computational and Systems Biology

    Coevolution-based prediction of key allosteric residues for protein function regulation

    Juan Xie, Weilin Zhang ... Luhua Lai
    Key allosteric residues are predicted based on sequence coevolution analysis, which serves as guidelines for allosteric drug design and optimization.
    1. Biochemistry and Chemical Biology
    2. Structural Biology and Molecular Biophysics

    Stimulation of the catalytic activity of the tyrosine kinase Btk by the adaptor protein Grb2

    Laura M Nocka, Timothy J Eisen ... John Kuriyan
    The adaptor protein Grb2 is able to enhance the activity of the cytoplasmic tyrosine kinase Btk through a novel mechanism, revealing a new role for Grb2 in B-cell signaling.
    1. Biochemistry and Chemical Biology
    2. Structural Biology and Molecular Biophysics

    The structural basis of the multi-step allosteric activation of Aurora B kinase

    Dario Segura-Peña, Oda Hovet ... Nikolina Sekulic
    An entropy switch controls the Aurora B autoactivation process through two distinct kinetic steps of phosphorylation.
    1. Biochemistry and Chemical Biology
    2. Structural Biology and Molecular Biophysics

    Allosteric activation or inhibition of PI3Kγ mediated through conformational changes in the p110γ helical domain

    Noah J Harris, Meredith L Jenkins ... John E Burke
    Regulation of phosphoinositide 3 kinase (PI3Kγ) is essential in immune function, and stimuli that modulate the dynamics of the PI3Kγ helical domain can activate or inhibit kinase activity.
    1. Biochemistry and Chemical Biology
    2. Immunology and Inflammation

    A back-door insight into the modulation of Src kinase activity by the polyamine spermidine

    Sofia Rossini, Marco Gargaro ... Giada Mondanelli
    A road to modulators of the kinase activity and the non-enzymatic functions of Src and IDO1 at once.
    1. Biochemistry and Chemical Biology
    2. Cell Biology

    Phosphorylation of tyrosine 90 in SH3 domain is a new regulatory switch controlling Src kinase

    Lenka Koudelková, Markéta Pelantová ... Daniel Rösel
    The functional role of novel regulatory mechanism within prototypic oncogenic kinase c-Src is described with particular emphasis on cancer cell migration, invasiveness, oncogenic transformation, and multilevel regulation of Src itself.
    1. Biochemistry and Chemical Biology
    2. Neuroscience

    CaMKII autophosphorylation can occur between holoenzymes without subunit exchange

    Iva Lučić, Léonie Héluin ... Andrew JR Plested
    CaMKII is capable of spreading activity between holoenzymes without exchanging subunits.
    1. Computational and Systems Biology
    2. Evolutionary Biology

    Mechanistic and evolutionary insights into isoform-specific ‘supercharging’ in DCLK family kinases

    Aarya Venkat, Grace Watterson ... Natarajan Kannan
    Isoform-specific variations in doublecortin-like kinases offer a new framework for understanding kinome-wide modulation of protein stability and catalytic activity.
    1. Biochemistry and Chemical Biology

    An unconventional gatekeeper mutation sensitizes inositol hexakisphosphate kinases to an allosteric inhibitor

    Tim Aguirre, Gillian L Dornan ... Dorothea Fiedler
    A subtle mutation in the ATP-binding site of inositol hexakisphosphate kinases increases their conformational flexibility and thereby makes them susceptible to isozyme-selective, allosteric inhibition.
    1. Biochemistry and Chemical Biology
    2. Computational and Systems Biology

    Theoretical analysis reveals a role for RAF conformational autoinhibition in paradoxical activation

    Gaurav Mendiratta, Edward Stites
    Mathematical modeling shows how RAF inhibitors can actually activate RAF kinases by stabilizing RAF proteins in the conformation capable of dimerization.
    1. Computational and Systems Biology
    2. Structural Biology and Molecular Biophysics

    Myristoyl’s dual role in allosterically regulating and localizing Abl kinase

    Svenja de Buhr, Frauke Gräter
    The cellular membrane competes with Abl for myristoyl binding to stabilize the preactivated state and enhance allosteric activation.
    1. Biochemistry and Chemical Biology
    2. Structural Biology and Molecular Biophysics

    Allosteric regulation of kinase activity in living cells

    Shivani Sujay Godbole, Nikolay V Dokholyan
    Protein kinase dysregulation, implicated in various diseases via cell signaling pathways, can be therapeutically and experimentally managed through allosteric modulation, facilitated by a dynamic network of interactions, with computational techniques enabling precise control in live systems.
    1. Cell Biology
    2. Developmental Biology

    Ulk4 promotes Shh signaling by regulating Stk36 ciliary localization and Gli2 phosphorylation

    Mengmeng Zhou, Yuhong Han, Jin Jiang
    Phosphorylation of the pseudokinase Ulk4 by Stk36 promotes primary ciliary tip localization of both proteins to facilitate the phosphorylation and activation of Gli in response to Sonic hedgehog.
    1. Biochemistry and Chemical Biology

    Unveiling the domain-specific and RAS isoform-specific details of BRAF kinase regulation

    Tarah Elizabeth Trebino, Borna Markusic ... Zhihong Wang
    An in-depth binding profile analysis of BRAF domains related to RAF activation and autoinhibition unveils the distinctive roles of each domain in selecting preferred RAS isoforms and facilitating autoinhibition.
    1. Cell Biology

    Location, location, location: Protein kinase nanoclustering for optimised signalling output

    Rachel S Gormal, Ramon Martinez-Marmol ... Frédéric A Meunier
    This article reviews the latest studies that have used super-resolution microscopy and cluster analysis methodologies to study the mechanism of protein kinase signalling hubs and their organisation at nanoscale.
    1. Computational and Systems Biology
    2. Immunology and Inflammation

    A kinase to cytokine explorer to identify molecular regulators and potential therapeutic opportunities

    Marina Chan, Yuqi Kang ... Taranjit S Gujral
    KinCytE is a web-based platform that explores kinase-cytokine-driven signaling and its relevance to understanding and treating diseases linked to disruptions in these pathways.
    1. Biochemistry and Chemical Biology
    2. Structural Biology and Molecular Biophysics

    Phosphorylation, disorder, and phase separation govern the behavior of Frequency in the fungal circadian clock

    Daniyal Tariq, Nicole Maurici ... Brian R Crane
    The intrinsic disorder of the circadian clock protein Frequency organizes binding partners, facilitates liquid–liquid phase separation, modulates Frequency phosphorylation, and derives from sequence properties conserved with homologous clock components.
    1. Biochemistry and Chemical Biology
    2. Microbiology and Infectious Disease

    Purine nucleosides replace cAMP in allosteric regulation of PKA in trypanosomatid pathogens

    Veronica Teresa Ober, George Boniface Githure ... Michael Boshart
    A minimal subset of two to three residues in cyclic nucleotide binding (CNB) domains controls nucleoside vs. cyclic nucleotide specificity, repurposing PKA of certain pathogens for novel nucleoside signaling pathways or sensing.
    1. Biochemistry and Chemical Biology

    Conformation selection by ATP-competitive inhibitors and allosteric communication in ERK2

    Jake W Anderson, David Vaisar ... Natalie G Ahn
    New ATP-competitive inhibitors show properties of conformation selection when complexed with the MAP kinase, ERK2, altering movements around the activation loop.
    1. Cancer Biology
    2. Structural Biology and Molecular Biophysics

    The molecular basis of Abelson kinase regulation by its αI-helix

    Johannes Paladini, Annalena Maier ... Stephan Grzesiek
    High-resolution NMR data and precise kinase activity assays on Abelson kinase bearing mutations in its αI-helix identify the αI-helix parts involved in disassembly of Abelson’s regulatory core and kinase activation.
    1. Structural Biology and Molecular Biophysics

    Structural dynamics of the active HER4 and HER2/HER4 complexes is finely tuned by different growth factors and glycosylation

    Raphael Trenker, Devan Diwanji ... Natalia Jura
    Cryo-EM structures uncover glycosylation in the ectodomains of full-length HER4 homodimer and HER2/HER4 heterodimer complexes, revealing how the binding of various growth factors alters dynamics at the dimerization interface.
    1. Biochemistry and Chemical Biology

    Molecular dissection of PI3Kβ synergistic activation by receptor tyrosine kinases, GβGγ, and Rho-family GTPases

    Benjamin R Duewell, Naomi E Wilson ... Scott D Hansen
    Single molecule reconstitution of PI3Kβ synergistic activation reveals mechanism for rapid PI(3,4,5)P3 production during immune cell signaling.
    1. Cancer Biology

    Recording and classifying MET receptor mutations in cancers

    Célia Guérin, David Tulasne
    Classification of MET mutations allows a better understanding of sensitivity and resistance to targeted therapies used in cancer.
    1. Biochemistry and Chemical Biology
    2. Structural Biology and Molecular Biophysics

    Allosteric coupling asymmetry mediates paradoxical activation of BRAF by type II inhibitors

    Damien M Rasmussen, Manny M Semonis ... Nicholas M Levinson
    A comprehensive allosteric model describes how inhibitors can activate rather than inhibit a target kinase by selectively driving formation of kinase dimers with one inhibited and one activated subunit.
    1. Structural Biology and Molecular Biophysics

    The αC-β4 loop controls the allosteric cooperativity between nucleotide and substrate in the catalytic subunit of protein kinase A

    Cristina Olivieri, Yingjie Wang ... Gianluigi Veglia
    The αC-β4 loop emerges as a hot spot for tuning allosteric cooperativity in the catalytic subunit of protein kinase A.

Contributors

  1. Volker Dötsch
    Senior Editor
  2. Amy H Andreotti
    Senior Editor
  3. Martin Eilers
    Reviewing Editor
  4. Maddy Parsons
    Reviewing Editor
  5. Natalia Jura
    Guest Editor
  6. Stefan Knapp
    Guest Editor
  7. James Murphy
    Guest Editor
  8. Takeo Saneyoshi
    Guest Editor
  9. Kathleen Gould
    Guest Editor
  10. Sierra Cullati
    Guest Editor