Kinases articles within Nature Communications

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  • Article
    | Open Access

    RAF family kinases transmit signals from activated RAS at the plasma membrane to downstream kinases to control cell proliferation, differentiation and survival. Here the authors shed light on the molecular mechanisms whereby small molecule RAF inhibitors induce RAS-RAF association and paradoxical RAF activation.

    • Ting Jin
    • , Hugo Lavoie
    •  & Marc Therrien

  • Article
    | Open Access

    Pseudokinases lack kinase activity, yet they impact cellular physiology through the regulation of bona fide signaling kinases. Here the authors describe the structure of the SgK223 pseudokinase and its adjacent domains, and identify regulatory interfaces required for self-assembly and downstream signaling.

    • Onisha Patel
    • , Michael D. W. Griffin
    •  & Isabelle S. Lucet

  • Article
    | Open Access

    The yeast Hsp70 homolog Ssb is a chaperone that binds translating ribosomes where it is thought to function primarily by promoting nascent peptide folding. Here the authors find that the ribosome biogenesis defect associated with the loss of Ssb is attributable to a specific disruption in TORC1 signaling rather than defects in ribosomal protein folding.

    • Kaivalya Mudholkar
    • , Edith Fitzke
    •  & Sabine Rospert

  • Article
    | Open Access

    Brown and beige adipose tissues dissipate heat via uncoupling protein 1 (UCP1). Here the authors show that the stress activated kinase MKK6 acts as a repressor of UCP1 expression, suggesting that its inhibition promotes adipose tissue browning and increases organismal energy expenditure.

    • Nuria Matesanz
    • , Edgar Bernardo
    •  & Guadalupe Sabio

  • Article
    | Open Access

    The Hippo tumor suppressor pathway is essential for development and tissue growth control. Here the authors employ a multi-disciplinary approach to characterize the interactions of the three Hippo kinases with the signaling adaptor MOB1 and show how they differently affect development, tissue growth and tumor suppression.

    • Yavuz Kulaberoglu
    • , Kui Lin
    •  & Alexander Hergovich

  • Article
    | Open Access

    AMPK is involved in sensing of metabolic stress. The authors show that the autophagy initiator ULK1 phosphorylates β1-Ser108 on the regulatory β1-subunit, sensitizing AMPK to allosteric drugs, and activates signaling pathways that appear independent of Thr172 phosphorylation in the kinase activation loop.

    • Toby A. Dite
    • , Naomi X. Y. Ling
    •  & Jonathan S. Oakhill

  • Article
    | Open Access

    Protein kinases are promising drug targets for treatment of malaria. Here, starting with a medicinal chemistry approach, Baker et al. generate an imidazopyridine that selectively targets Plasmodium falciparum PKG, inhibits blood stage parasite growth in vitro and in mice and blocks transmission to mosquitoes.

    • David A. Baker
    • , Lindsay B. Stewart
    •  & Simon A. Osborne

  • Article
    | Open Access

    Sensor histidine kinases (SHK) consist of sensor, linker and kinase modules and different models for SHK signal transduction have been proposed. Here the authors present nano- to millisecond time-resolved X-ray scattering measurements, which reveal a structural mechanism for kinase domain activation in SHK.

    • Oskar Berntsson
    • , Ralph P. Diensthuber
    •  & Sebastian Westenhoff

  • Article
    | Open Access

    Calcium dependent protein kinase 1 (CDPK1) plays an important role in asexual development of Plasmodium falciparum. Using phosphoproteomics and conditional knockdown of CDPK1, the authors here identify CDPK1 substrates and a cross-talk between CDPK1 and PKA, and show the role of CDPK1 in parasite invasion.

    • Sudhir Kumar
    • , Manish Kumar
    •  & Pushkar Sharma

  • Article
    | Open Access

    Ca2+/calmodulin-dependent protein kinase II (CaMKII) forms a 12 subunit holoenzyme central to synaptic plasticity. Here the authors report a 3D structure of the CaMKII holoenzyme in an activation-competent state obtained by single particle EM, and suggest a role for the intrinsically disordered linker domain in facilitating cooperative activation.

    • Janette B. Myers
    • , Vincent Zaegel
    •  & Steve L. Reichow

  • Article
    | Open Access

    ATP-binding cassette (ABC) transporters hydrolyse ATP to transport molecules across the cell membrane. Here Vogelet al. show that the ABC exporter MsBA can couple ATP hydrolyse to an adenylate kinase activity that seems to be predominant at low ATP levels and a general feature of ABC exporters.

    • Hundeep Kaur
    • , Andrea Lakatos-Karoly
    •  & Clemens Glaubitz

  • Article
    | Open Access

    Raising cellular levels of the metabolic cofactor NAD+ reverses key indicators of aging. Here, Ratajczak et al. show that cellular levels of NAD+ depend on the extracellular catalytic activity of NRK1, which processes two NAD+precursors, nicotinamide mononucleotide and nicotinamide riboside, in mice.

    • Joanna Ratajczak
    • , Magali Joffraud
    •  & Carles Cantó

  • Article
    | Open Access

    The stressosome is a multiprotein complex that regulates the expression of stress response genes in Gram-positive bacteria. Here the authors characterize a stressosome from a Gram-negative bacterium, showing that one of the protein components senses oxygen through a bound haem.

    • Xin Jia
    • , Jian-bo Wang
    •  & Emily E. Weinert

  • Article
    | Open Access

    Phosphorylation of L-type calcium CaV channels by protein kinase A is essential for several physiological events. Here, the authors show how this kinase regulates CaV1.4 activity, suggesting a general regulatory mechanism for all L-type calcium channels.

    • Lingjie Sang
    • , Ivy E. Dick
    •  & David T. Yue

  • Article
    | Open Access

    Claspin mediates the transmission of a replication-stress signal from ATR to Chk1 and is necessary for efficient fork progression. Here the authors demonstrate that the C-terminal acidic patch is important for this role due to its interaction with Cdc7.

    • Chi-Chun Yang
    • , Masahiro Suzuki
    •  & Hisao Masai

  • Article
    | Open Access

    Squamous epithelia present actin-rich microridges on the apical surface, but the mechanism of their formation is not known. Here the authors show that, in zebrafish epidermis, the exclusion of the basolateral regulator Lgl from the apical domain by atypical protein kinase C prevents precocious elongation and fusion of microridges.

    • Renuka Raman
    • , Indraneel Damle
    •  & Mahendra Sonawane

  • Article
    | Open Access

    The ataxia-telangiectasia mutated (ATM) protein kinase is a key player in the response to DNA damage and is essential for the maintenance of cellular homeostasis. Here the authors describe the cryo-EM structure of ATM/Tel1 from fission yeast that suggests how dimerization regulates its activity.

    • Xuejuan Wang
    • , Huanyu Chu
    •  & Gang Cai

  • Article
    | Open Access

    Phytochromes regulate plant responses to environmental light conditions but despite extensive research the initial events in phytochrome signaling remain uncertain. Here, Shin et al. provide evidence that phytochrome phosphorylates target proteins via kinase activity in the N-terminal core domain.

    • Ah-Young Shin
    • , Yun-Jeong Han
    •  & Jeong-Il Kim

  • Article
    | Open Access

    The membrane-bound kinase CckA controls the activity of the Caulobacter crescentusmaster regulator CtrA, which in turn coordinates asymmetric cell division. Here, the authors show that CckA contains two sensory domains that have distinct sensitivities to fluctuations in cyclic-di-GMP concentration and subcellular niche.

    • Thomas H. Mann
    • , W. Seth Childers
    •  & Lucy Shapiro

  • Article
    | Open Access

    Kinase inhibitors are important drugs and usually target the ATP binding pocket of kinases. Here, Kii et al.report a completely new type of kinase inhibitor that specifically targets the protein folding intermediate state, but not the mature form, of the protein kinase DYRK1A.

    • Isao Kii
    • , Yuto Sumida
    •  & Masatoshi Hagiwara

  • Article
    | Open Access

    Antibiotic resistance is a major clinical problem that threatens to undermine our ability to control infectious diseases. Here the authors present detailed structural analysis of Rifampin phosphotransferase from Listeria monocytogenes, yielding insight on how this class of enzyme inactivates its target antibiotics.

    • Peter J. Stogios
    • , Georgina Cox
    •  & Gerard D. Wright

  • Article
    | Open Access

    Aurora A is a protein kinase that contributes to the progression of mitosis by stimulating microtubule nucleation. Here the authors show that Aurora A also functions during T cell activation by maintaining TCR signaling through Lck activation.

    • Noelia Blas-Rus
    • , Eugenio Bustos-Morán
    •  & Francisco Sánchez-Madrid

  • Article
    | Open Access

    The target of rapamycin (Tor) is a Ser/Thr protein kinase that regulates a wide range of anabolic and catabolic processes. Here the authors describe a sub-nanometer cryo-EM structure of a yeast Tor–Lst8 complex and propose an overall topology that differs from that previously suggested for mTORC1.

    • Domagoj Baretić
    • , Alex Berndt
    •  & Roger L. Williams

  • Article
    | Open Access

    Ras signalling through PI3K kinase has an important role in tumour initiation and progression. Here, the authors show that the interaction of Ras with PI3-Kinase p110α and the subsequent activation of Rac-GTPase impairs cell -cell interaction by blocking the downstream Reelin/E-cadherin, thus resulting in cell migration.

    • Esther Castellano
    • , Miriam Molina-Arcas
    •  & Julian Downward

  • Article
    | Open Access

    The protein kinase ASK1 has been linked to cellular stress responses. Here the authors show that ASK1 also regulates gene expression and activity of beige and brown adipocytes, and demonstrate adipocyte ASK1 has a physiological role in regulating thermogenesis in mice.

    • Kazuki Hattori
    • , Isao Naguro
    •  & Hidenori Ichijo

  • Article
    | Open Access

    Natural killer cells of acute myeloid leukaemia patients lack cytotoxic activity. Here the authors show that these cells have elevated GSK3β, and that its inhibition prolongs survival of mice transplanted with human AML and stimulates NK cytotoxicity via increased adhesion of NK cells to their targets.

    • Reshmi Parameswaran
    • , Parameswaran Ramakrishnan
    •  & David N. Wald

  • Article
    | Open Access

    Ternary complex (TC) and eIF4F complex assembly are rate-limiting steps in translation initiation that are regulated by eIF2α phosphorylation and the mTOR/4E-BP pathway. Here the authors show that the protein kinases mTORC1 and CK2 coordinate TC and eIF4F complex assembly through eIF2β to stimulate cell proliferation.

    • Valentina Gandin
    • , Laia Masvidal
    •  & Ivan Topisirovic

  • Article
    | Open Access

    Therapies are needed for the prevention of chondrocyte hypertrophy and thinning of articular cartilage, features of osteoarthritic joint destruction. Here, the authors show that interfering with Sik3 signalling can increase the size of the chondrocyte population and reduce severity of a surgically induced mouse model of osteoarthritis.

    • Yasuhito Yahara
    • , Hiroshi Takemori
    •  & Noriyuki Tsumaki

  • Article
    | Open Access

    Organic cation transporters are important drug transporters that influence therapeutic outcomes. Here, the authors find that these transporters are regulated by tyrosine phosphorylation and propose that tyrosine kinase inhibitors can influence drug transporter function through post-translational mechanisms.

    • Jason A. Sprowl
    • , Su Sien Ong
    •  & Navjotsingh Pabla

  • Article
    | Open Access

    The Tec family tyrosine kinase, Itk, is a component of the T-cell receptor essential for optimal Th2 responses in vivo. Here the authors show in human cells and mouse models that Itk is also needed for the production of IL-9, an important contributor to allergic asthma.

    • Julio Gomez-Rodriguez
    • , Françoise Meylan
    •  & Pamela L. Schwartzberg

  • Article
    | Open Access

    Protein kinase R (PKR) has been suggested to act as a mediator of ER stress and inflammation in obesity. Here, Lancaster et al. find that genetic loss of PKR does not alter the development of obesity, and suggest that the use of littermate controls may explain differences in mouse knockout phenotypes.

    • G. I. Lancaster
    • , H. L. Kammoun
    •  & M. A. Febbraio

  • Article
    | Open Access

    Autophagosome biogenesis is initiated by recruitment of Atg9-vesicles to the phagophore assembly site. Here Rao et al. use a reconstituted in vitrosystem to describe the mechanism by which activation of the Atg1-kinase complex from its constituent parts recruits and tethers Atg9-vesicles.

    • Yijian Rao
    • , Marco G. Perna
    •  & Thomas Wollert

  • Article
    | Open Access

    Diacylglycerol kinase is a small bacterial membrane-bound trimer that catalyses diacylglycerol conversion to phosphatidic acid. Here, the authors solve the crystal structure of the kinase bound to a lipid substrate and an ATP analogue, and show that the active site arose through convergent evolution.

    • Dianfan Li
    • , Phillip J. Stansfeld
    •  & Martin Caffrey

  • Article
    | Open Access

    TANK binding kinase 1 (TBK1) is a non-canonical IκB kinase that regulates immunity via NF-κB. Here Pillai et al. show that TBK1 localizes to centrosomes during mitosis, and regulates microtubule dynamics and spindle formation by phosphorylating the centrosomal protein CEP170 and the mitotic apparatus protein NuMa.

    • Smitha Pillai
    • , Jonathan Nguyen
    •  & Srikumar Chellappan

  • Article
    | Open Access

    The SAD kinases contain a UBA domain that binds to the kinase domain and has a role in autoinhibition and allosteric activation of the AMPK homoenzyme. Here, the authors identify an autoinhibitory sequence in SAD and show that the UBA domain synergistically functions as an autoinhibitory domain.

    • Jing-Xiang Wu
    • , Yun-Sheng Cheng
    •  & Jia-Wei Wu

  • Article
    | Open Access

    Rho kinases regulate the actin cytoskeleton by controlling stress fibre formation. Truebestein et al.show that the length of its coiled-coil determines ROCK2 function, and propose that the coiled coil acts as a spacer, targeting kinase activity to a discrete distance from the membrane.

    • Linda Truebestein
    • , Daniel J. Elsner
    •  & Thomas A. Leonard

  • Article
    | Open Access

    PAK4 is a metazoan-specific kinase, which acts downstream of the cell polarity regulator Cdc42. Here, Baskaran et al.determine the structure of PAK4 bound to the endogenous inhibitor Inka1 from crystals that form spontaneously in mammalian cells overexpressing both proteins.

    • Yohendran Baskaran
    • , Khay C. Ang
    •  & Robert C. Robinson

  • Article
    | Open Access

    NEK7, a kinase involved in mitosis, is regulated by the kinase NEK9. Here the authors identify the region in NEK9 that binds NEK7 and find that the mechanism of regulation involves dimerization coupled to structural changes in the active site.

    • Tamanna Haq
    • , Mark W. Richards
    •  & Richard Bayliss

  • Article
    | Open Access

    The issue whether the cell surface protein c-kit identifies resident cardiac stem cells (CSC) is controversial. By using novel reporter mouse models, Sultana et al. show that c-kit+cells represent a subpopulation of endothelial cells in the developing and adult heart and do not exhibit CSC traits in health or disease.

    • Nishat Sultana
    • , Lu Zhang
    •  & Chen-Leng Cai

  • Article
    | Open Access

    A variety of signals have been reported to either activate or inhibit the Hippo kinase cascade. Here, Meng et al. show that mitogen activated protein kinase kinase kinase kinase (MAP4K) family members function in parallel to and are partially redundant with MST1/2 in regulating LATS in response to upstream signals.

    • Zhipeng Meng
    • , Toshiro Moroishi
    •  & Kun-Liang Guan

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