Kinases articles within Nature Communications

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  • 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

  • Article
    | Open Access

    Components of the Hippo signalling pathway localize to apical junctions in epithelial cells, where they regulate growth in response to mechanical and biochemical cues. Sun et al. show that these proteins are organized into distinct junctional complexes, which reorganize up on Hippo pathway activation.

    • Shuguo Sun
    • , B. V. V. G. Reddy
    •  & Kenneth D. Irvine

  • Article
    | Open Access

    The prolonged presence of cytokines is necessary to produce a robust pro-inflammatory response through the activation of p38 MAPK. Here, Tomidaet al. show that asynchronous oscillatory activation of p38 MAPK occurs at the single-cell level and is necessary for the proper expression of pro-inflammatory genes.

    • Taichiro Tomida
    • , Mutsuhiro Takekawa
    •  & Haruo Saito

  • Article
    | Open Access

    In response to brain injury, microglia extend processes to isolate the lesion. Here Choi et al. show that microglia expressing a pathogenic mutation in the Parkinson’s disease-associated LRRK2 gene show reduced motility and delayed lesion isolation in vitro and in vivodue to attenuated focal adhesion kinase activity.

    • Insup Choi
    • , Beomsue Kim
    •  & Eun-Hye Joe

  • Article
    | Open Access

    Integrin-linked kinase (ILK) is known to modulate the extracellular matrix and hair follicle morphogenesis. Here, Morgner et al.show that lack of ILK causes an aberrant ratio of basement membrane laminins, activating stem cells and predisposing skin to carcinogenesis.

    • Jessica Morgner
    • , Sushmita Ghatak
    •  & Sara A. Wickström

  • Article
    | Open Access

    Tumors hijack cellular pathways to evade the effects of cancer therapy. Here, Advaniet al. show that DNA damage-induced phosphorylation of CRAF Serine 338 triggers DNA repair by recruiting CHK2, highlighting a role for CRAF independent from its canonical function as a kinase.

    • Sunil J. Advani
    • , Maria Fernanda Camargo
    •  & David A. Cheresh

  • Article
    | Open Access

    Receptor tyrosine kinases are key mediators of cell proliferation that have been implicated in several disease states for which they represent promising drug targets. Here the authors determine the thermodynamic basis for the low propensity of FGFR1 to access the DFG-Phe-out conformation required to bind type-II inhibitors.

    • Tobias Klein
    • , Navratna Vajpai
    •  & Alexander L. Breeze

  • Article |

    mTOR signalling regulates protein synthesis in response to changes in nutrient availability. Chang et al.demonstrate that mTOR can stimulate translation by promoting the shortening of mRNA 3′-untranslated regions, and that expression of ubiquitin ligases is selectively enhanced by this mechanism.

    • Jae-Woong Chang
    • , Wei Zhang
    •  & Jeongsik Yong

  • Article
    | Open Access

    Lipid droplets (LDs) supply fatty acids to cellular processes and move bidirectionally on microtubules. Here the authors show that nutrient starvation causes dispersal of mitochondria and LD to the periphery of the cell along detyrosinated microtubules and increases LD–mitochondria interactions in an AMPK-dependent manner.

    • Albert Herms
    • , Marta Bosch
    •  & Albert Pol

  • Article |

    Some normal and cancer stem cells are resistant to killing by genotoxins, but the mechanism for this resistance is poorly understood. Here the authors show that adult stem cells inDrosophila melanogastergermline and midgut are resistant to genotoxic stimuli and find that this is mediated by signalling via the receptor tyrosine kinase Tie released from apoptotic cells.

    • Yalan Xing
    • , Tin Tin Su
    •  & Hannele Ruohola-Baker

  • Article |

    Mammalian female meiosis is error prone, with error rates increasing with age. Here Touati et al. show that the spindle assembly checkpoint (SAC) protein BubR1, which decreases with age, has multiple roles in meiosis I by controlling SAC, stabilizing the mitotic spindle and timing the onset of anaphase I.

    • Sandra A. Touati
    • , Eulalie Buffin
    •  & Katja Wassmann

  • Article |

    Chaperone-mediated autophagy (CMA) helps maintain protein quality during cellular stress. Here the authors show that CMA is also activated in response to DNA damage and regulates degradation of the cell cycle regulator Chk1—the first nuclear protein shown to be a substrate of CMA.

    • Caroline Park
    • , Yousin Suh
    •  & Ana Maria Cuervo

  • Article |

    In contrast to most receptor tyrosine kinases, the insulin and insulin-like growth factor-1 receptors are preformed, disulfide-linked dimers. Here the authors show that, after the two kinase domains of IR and IGF1R undergo autophosphorylation, they form a specific dimer to phosphorylate downstream substrates.

    • M. Zulema Cabail
    • , Shiqing Li
    •  & W. Todd Miller

  • Article |

    Abl is a cytoplasmic tyrosine kinase important for growth, whose hyper activation is associated with several types of cancers. Here, the authors use recombinant Abl protein to uncover the molecular mechanism underlying allosteric activation of Abl by its SH2 domain through the regulation of autophosphorylation.

    • Allan Joaquim Lamontanara
    • , Sandrine Georgeon
    •  & Oliver Hantschel

  • Article |

    Inositol trisphosphate kinases (IP3Ks) and inositol hexakisphosphate kinases (IP6Ks) are involved in signalling by phosphorylating their specific targets. Here, Wang et al.report the crystal structure of a hybrid IP6K/IP3K enzyme, analyse the substrate orientations and propose an evolutionary trajectory for this kinase family.

    • Huanchen Wang
    • , Eugene F. DeRose
    •  & Stephen B. Shears

  • Article
    | Open Access

    Type II PI4-kinase dysfunction is associated with diseases including cancer and Alzheimer's disease; however, the development of specific modulators has been hampered by a lack of structural information. Zhou et al. present the crystal structure of PI4KIIα in its ADP-bound form, providing insight into its regulation.

    • Qiangjun Zhou
    • , Jiangmei Li
    •  & Chang Chen

  • Article
    | Open Access

    Cyclin-dependent kinase 12 (Cdk12) phosphorylates the C-terminal domain (CTD) of RNA polymerase II to regulate transcription. Here, the authors solve the crystal structure of the Cdk12 kinase domain and show that Cdk12 has its highest activity on a CTD substrate that carries a serine 7 phosphorylation.

    • Christian A. Bösken
    • , Lucas Farnung
    •  & Matthias Geyer

  • Article |

    The phosphorylation of proteins is a common mechanism for signal transduction. Here, the authors present a structural analysis of a histidine kinase in the process of autophosphorylation, helping to elucidate the catalytic mechanism.

    • Patricia Casino
    • , Laura Miguel-Romero
    •  & Alberto Marina

  • Article |

    Spitzoid neoplasms constitute a spectrum of melanocytic tumours, characterized by distinct clinical, pathological and genetic features. Here, Wiesner et al. show that kinase fusions represent the majority of oncogenic aberrations in spitzoid neoplasms and may serve as therapeutic targets for metastatic spitzoid melanoma.

    • Thomas Wiesner
    • , Jie He
    •  & Boris C. Bastian

  • Article
    | Open Access

    Despite the central importance of NADP+ in mitochondrial energy metabolism, no NAD kinase has been found in human mitochondria to synthesize NADP+. These authors show C5orf33, a protein specific to animals and protists, to be the missing NAD kinase and demonstrate its mitochondrial localization and activity.

    • Kazuto Ohashi
    • , Shigeyuki Kawai
    •  & Kousaku Murata

  • Article
    | Open Access

    G-protein-coupled receptors sense extracellular cues and transmit the signal to distinct trimeric G-proteins. Stefanet al.show that in response to cAMP, a central and conserved component of the Gαs-coupled receptor cascade, the RII subunit of PKA, specifically binds to and participates in Gαi signaling.

    • Eduard Stefan
    • , Mohan K. Malleshaiah
    •  & Stephen W. Michnick

  • Article |

    The kinase Dyrk1A is essential for brain function and development, and its excessive activity has been implicated in Down syndrome. In this study, a selective inhibitor of Dyrk1A is developed, which may help to elucidate the molecular mechanisms of normal and diseased brain.

    • Yasushi Ogawa
    • , Yosuke Nonaka
    •  & Masatoshi Hagiwara

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