Kinases articles within Nature Communications

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  • Article
    | Open Access

    Diamond Blackfan Anemia (DBA) is a congenital bone marrow failure syndrome that is associated with anemia. Here, the authors examine the role of Nemo-like kinase (NLK) in erythroid cells in the pathogenesis of DBA and as a potential target for therapy.

    • M. C. Wilkes
    • , K. Siva
    •  & K. M. Sakamoto

  • Article
    | Open Access

    Chemical tools to monitor drug-target engagement of endogenous enzymes are essential for preclinical target validation. Here, the authors present a chemical genetics strategy to study target engagement of endogenous kinases, achieving specific labeling and inactivation of FES kinase to provide insights into FES’ role in neutrophil phagocytosis.

    • Tom van der Wel
    • , Riet Hilhorst
    •  & Mario van der Stelt

  • Article
    | Open Access

    Cyclin-dependent kinase (CDK) inhibitors are widely used both in the clinic and for basic research aimed at dissecting the specific cellular functions of specific CDKs. Here, the authors report the development of a panel of fluorescent reporter probes and provide a comprehensive profile of the inhibitory activity of several CDK inhibitors towards all 21 CDKs in living cells.

    • Carrow I. Wells
    • , James D. Vasta
    •  & Matthew B. Robers

  • Article
    | Open Access

    Identifying kinases responsible for specific phosphorylation events remains challenging. Here, the authors leverage kinase inhibitor profiles for the identification of kinase-substrate site pairs in cell extracts, developing a method that can identify the enzymes responsible for unassigned phosphorylation events.

    • Nikolaus A. Watson
    • , Tyrell N. Cartwright
    •  & Jonathan M. G. Higgins

  • Article
    | Open Access

    In mitosis, Aurora B switches substrate specificity in response to phosphorylation of S227 in the activation loop by a cell cycle-processed active fragment of PKCε. Here, the authors show that this switch protects from chromosome non-disjunction by delaying anaphase entry and promoting TopoIIα-dependent resolution.

    • Joanna R. Kelly
    • , Silvia Martini
    •  & Tanya N. Soliman

  • Article
    | Open Access

    AMPK integrates information about a cell’s energy status to inform decisions about cellular processes, including autophagy. Here the authors identify cyclin Y as an AMPK substrate, which phosphorylates cyclin Y and promotes its interaction with CDK16 to stimulate autophagy.

    • Marc Dohmen
    • , Sarah Krieg
    •  & Jörg Vervoorts

  • Article
    | Open Access

    IKK2 is the main mediator of the NF-kappaB pathway. Here, the authors demonstrate that LMP1 sustains the survival of Epstein-Barr virus-transformed human B cells and post-transplant lymphoma through IKK2 that induces JNK signaling through TPL2.

    • Stefanie Voigt
    • , Kai R. Sterz
    •  & Arnd Kieser

  • Article
    | Open Access

    mTORC2 activates Akt, a regulator of cell growth and metabolism, however, the role of mTORC2 in adipocytes is incompletely understood. Here the authors report that a mTORC2-Akt axis specifically activates ACLY to promote lipid synthesis and histone acetylation during brown adipocyte differentiation.

    • C. Martinez Calejman
    • , S. Trefely
    •  & D. A. Guertin

  • Article
    | Open Access

    Here, Bhattacharya et al. chemically mutagenize Leishmania and identify genes associated with resistance to miltefosine and paromomycin by next generation sequencing. The study shows that a protein kinase (CDPK1) can mediate resistance to paromomycin by affecting translation.

    • Arijit Bhattacharya
    • , Philippe Leprohon
    •  & Marc Ouellette

  • Article
    | Open Access

    The chromosomal kinase JIL-1 is responsible for interphase histone H3S10 phosphorylation and has been proposed to protect active chromatin from heterochromatinisation. Here, the authors show that JIL-1 is stabilized and anchored to active genes and telomeric transposons by JASPer, which binds to H3K36me3 nucleosomes via its PWWP domain.

    • Christian Albig
    • , Chao Wang
    •  & Catherine Regnard

  • Article
    | Open Access

    The ERK signalling pathway is activated in many cancers, however ERK1 and ERK2 are difficult to target pharmacologically. Here, the authors identify a small molecule inhibitor that binds covalently to the D-recruitment site of ERK and induces cell death and reduces tumour growth in mice.

    • Tamer S. Kaoud
    • , William H. Johnson
    •  & Kevin N. Dalby

  • Article
    | Open Access

    Regulation of post translational modification of 53BP1 is critical for genome integrity and regulation of DNA damage response. Here the authors reveal a CDK5-PP4 phospho-signaling cascade that leads 53BP1 to sites of DNA damage.

    • Xiao-Feng Zheng
    • , Sanket S. Acharya
    •  & Dipanjan Chowdhury

  • Article
    | Open Access

    Protein kinase A (PKA) is a cyclic nucleotide dependent protein kinase. Here the authors use single molecule optical tweezers and steered molecular dynamic simulations to follow in real time and quantitatively characterize the signals transduced by cAMP through the structure of the PKA regulatory subunit, and propose a model for PKA allosteric activation.

    • Yuxin Hao
    • , Jeneffer P. England
    •  & Rodrigo A. Maillard

  • Article
    | Open Access

    The inner centromere protein (INCENP) activates Aurora kinase B (AURKB) and Aurora kinase C. Here the authors provide insights into the activation mechanism of AURKB/C by determining the crystal structure of fully active phosphorylated human AURKC bound to the phosphorylated C-terminal IN-box section of human INCENP.

    • Kamal R. Abdul Azeez
    • , Sneha Chatterjee
    •  & Jonathan M. Elkins

  • Article
    | Open Access

    β-propeller domains are an important class of folding substrates for the eukaryotic cytosolic chaperonin CTT. Here the authors find that CTT contributes to the folding and assembly of two β-propeller proteins from mTOR complexes, mLST8 and Raptor, and determine the 4.0 Å cryoEM structure of a human mLST8-CCT intermediate that shows mLST8 in a near-native state.

    • Jorge Cuéllar
    • , W. Grant Ludlam
    •  & José M. Valpuesta

  • Article
    | Open Access

    Colorectal cancer cells can acquire resistance to MEK inhibition due to BRAF or KRAS amplification. Here, the authors show that while MEK inhibitor withdrawal in BRAF mutant cells restores sensitivity to the inhibitor through the loss of BRAF amplification mediated by a p57-dependent mechanism, drug withdrawal from KRAS mutant cells does not restore sensitivity but results in EMT and chemoresistance.

    • Matthew J. Sale
    • , Kathryn Balmanno
    •  & Simon J. Cook

  • Article
    | Open Access

    During centriole duplication, Plk4 regulates formation of a single daughter centriole adjacent to the mother centriole, but the mechanism is unclear. Here, the authors show that Plk4 can undergo liquid–liquid phase separation and that the condensation properties are regulated by autophosphorylation.

    • Shohei Yamamoto
    •  & Daiju Kitagawa

  • Article
    | Open Access

    Hippo pathway inactivation plays a role in many cancers, although how tumor cells depress signaling is unclear. Here, Lim et al. identify STK25, which activates LATS in a manner distinct from other upstream kinases and is focally deleted from a range of human cancers.

    • Sanghee Lim
    • , Nicole Hermance
    •  & Neil J. Ganem

  • Article
    | Open Access

    Hyperactivation of Akt promotes tumorigenesis. Here, the authors show that SAV1, a member of Hippo signalling, interacts with Akt to suppress Akt activity and MERTK-mediated Akt phosphorylation relieves this suppression to facilitate Akt oncogenic activity in clear cell renal carcinomas.

    • Yao Jiang
    • , Yanqiong Zhang
    •  & Pengda Liu

  • Article
    | Open Access

    Protein kinase A (PKA) is typically activated by cAMP. Here, Bachmaier et al. show that PKA of Trypanosoma is activated by nucleoside-related ligands, explain the ligand selectivity swap by a co-crystal structure of trypanosome PKAR, and identify potential downstream targets by phosphoproteomics.

    • Sabine Bachmaier
    • , Yuri Volpato Santos
    •  & Michael Boshart

  • Article
    | Open Access

    The cell wall of Gram-positive bacteria consists of peptidoglycan modified with other polymers, such as the capsular polysaccharide. Here, the authors reconstitute the biosynthesis of capsular polysaccharide and elucidate its interplay with the cell wall biosynthetic machinery.

    • Marvin Rausch
    • , Julia P. Deisinger
    •  & Tanja Schneider

  • Article
    | Open Access

    Optical control over receptor tyrosine kinase (RTK) activity can find application in both basic biology and synthetic biology. Here the authors combine the photosensory module of DrBphP bacterial phytochrome with the Trk family of RTKs to obtain Trks that are reversibly switchable with near-infrared and far-red light.

    • Anna V. Leopold
    • , Konstantin G. Chernov
    •  & Vladislav V. Verkhusha

  • Article
    | Open Access

    Allosteric interactions are an important contributor to the catalytic properties of enzyme. Here the authors demonstrate—using the prototypical protein kinase PKA—that the allosteric cooperativity underscoring substrate recognition and product release are directly linked to changes in conformational entropy.

    • Yingjie Wang
    • , Manu V.S.
    •  & Gianluigi Veglia

  • Article
    | Open Access

    How the chromosome passenger complex (CPC) phosphorylates the kinetochores that can be a micron away to control mitotic events is unknown. Here the authors find that the CPC directly binds microtubules near inner centromeres, which controls its ability to phosphorylate kinetochores independently of tension generated by kinetochore microtubule attachments.

    • Prasad Trivedi
    • , Anatoly V. Zaytsev
    •  & P. Todd Stukenberg

  • Article
    | Open Access

    Beta II protein kinase C (βIIPKC) activation contributes to heart failure. Here the authors show, in a rat model of myocardial infarction, that heart failure outcome can be improved by selectively inhibiting the interaction between βIIPKC and its downstream mitochondrial target Mitofusin-1, and that this strategy is superior to global βIIPKC inhibition.

    • Julio C. B. Ferreira
    • , Juliane C. Campos
    •  & Daria Mochly-Rosen

  • Article
    | Open Access

    Bacterial histidine kinases (HKs) play key roles in the response to stimuli and are regulated by reversible phosphorylation. Here, the authors show that the activity of a HK in the plant pathogen Xanthomonas campestris is modulated by irreversible, proteolytic modification in response to osmostress.

    • Chao-Ying Deng
    • , Huan Zhang
    •  & Wei Qian

  • Article
    | Open Access

    The activity of several protein kinases is increased upon cellular production of reactive oxygen species, which can cause cysteine oxidation. Here the authors show that sulfenylation of specific cysteine residues within Src induce local structural changes that directly impact its activation.

    • David E. Heppner
    • , Christopher M. Dustin
    •  & Albert van der Vliet

  • Article
    | Open Access

    Dimethyl fumarate (DMF) is a major drug in the treatment of psoriasis and multiple sclerosis. Here the authors reveal a mechanism of RSK/MSK inhibition through covalent inhibition that can explain the observed clinical effects and the dose–response characteristics of DMF treatment.

    • Jacob Lauwring Andersen
    • , Borbala Gesser
    •  & Poul Nissen

  • Article
    | Open Access

    Despite functional optimisation during evolution of parasitism, most members of a calcium dependent protein kinase (CDPK) family show genetic redundancy in Plasmodium. Here, the authors screen 294 genetic interactions among protein kinases in Plasmodium and show how some CDPKs functionally interact to control motility and host cell invasion.

    • Hanwei Fang
    • , Ana Rita Gomes
    •  & Mathieu Brochet

  • Article
    | Open Access

    Female meiotic divisions are asymmetric with the formation of large oocytes and small polar bodies, thought to result from cortical spindle placement before anaphase. The authors find that Cdk1 inactivation triggers F-actin dependent post-anaphase spindle migration, resulting in cortical protrusion.

    • Zhe Wei
    • , Jessica Greaney
    •  & Hayden A. Homer

  • Article
    | Open Access

    Influenza A virus (IAV) causes annual epidemics and development of antivirals is needed. Here, the authors perform phosphoproteomics during IAV entry and identify GRK2 as drug target, inhibition of which decreases replication of seasonal and pandemic IAV in primary human cells and animal models.

    • Emilio Yángüez
    • , Annika Hunziker
    •  & Silke Stertz

  • Article
    | Open Access

    RIPK3-mediated phosphorylation of the mixed lineage kinase domain-like (MLKL) pseudokinase is thought to be the trigger for MLKL activation during necroptotic signaling. Here the authors provide evidence that the transition of human MLKL from a monomeric state to a tetramer is essential for necroptosis signalling.

    • Emma J. Petrie
    • , Jarrod J. Sandow
    •  & James M. Murphy

  • Article
    | Open Access

    Fam20 proteins are kinases that phosphorylate secreted proteins and proteoglycans. Here the authors present the crystal structures of the three Fam20 kinases and their complexes and give mechanistic insights into substrate recognition and the function and regulation of this kinase family.

    • Hui Zhang
    • , Qinyu Zhu
    •  & Junyu Xiao

  • Article
    | Open Access

    The human type 1 insulin-like growth factor receptor (IGF-1R) is important for normal human growth and development. Here, the authors present the crystal structures of the IGF-1R ectodomain both in its apo form and in complex with its ligand insulin-like growth factor I and discuss the receptor activation mechanism.

    • Yibin Xu
    • , Geoffrey K.-W. Kong
    •  & Michael C. Lawrence

  • Article
    | Open Access

    AMPK activation inhibits cardiac hypertrophy. Here the authors show that this occurs independently of previously proposed mechanisms and that AMPK controls the phosphorylation of the aminotransferase GFAT, thereby preventing cardiac hypertrophy through the reduction of protein O-GlcNAcylation.

    • Roselle Gélinas
    • , Florence Mailleux
    •  & Luc Bertrand

  • Article
    | Open Access

    The Hsp90 chaperone cycle is influenced by multiple phosphorylation events but their regulatory functions are poorly understood. Here, the authors show that phosphorylation and unfolding of cochaperone Cdc37 tailors the Hsp90 chaperone cycle by recruiting kinases that promote distinct phosphorylation patterns.

    • Ashleigh B. Bachman
    • , Dimitra Keramisanou
    •  & Ioannis Gelis

  • Article
    | Open Access

    New antibiotics with reduced potential for resistance are urgently needed. Here, the authors use a multidisciplinary approach to characterize substrate discrimination in macrolide resistance kinases and present a strategy for the prediction of mutations that expand the substrate range of antibiotic-inactivating enzymes.

    • Andrew C. Pawlowski
    • , Peter J. Stogios
    •  & Gerard D. Wright

  • Article
    | Open Access

    Src is a prototypical signaling non-receptor protein tyrosine kinase that interconverts between distinct conformations. Here the authors use variants of the kinase-inhibitor dasatinib to define three specific conformational states of the Src kinase and shed insight on the effect of conformation-specific inhibitors on Src dynamics.

    • Michael Tong
    • , Jeff G. Pelton
    •  & Markus A. Seeliger

  • Article
    | Open Access

    The Bcr-Abl tyrosine kinases p210 and p190 are linked to different leukemias and differ by the Dbl homology (DH) and Pleckstrin-homology (PH) domains. Here the authors characterize structures of the Bcr-Abl p210 DH and PH domains and find that the PH domain is important for the cellular localization and signaling network of p210.

    • Sina Reckel
    • , Charlotte Gehin
    •  & Oliver Hantschel

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