Kinases articles within Nature

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  • Article
    | Open Access

    Several independent lines of evidence demonstrated long-term potentiation induction by a structural function of calmodulin-dependent protein kinase II rather than by its enzymatic activity.

    • Jonathan E. Tullis
    • , Matthew E. Larsen
    •  & K. Ulrich Bayer

  • Article
    | Open Access

    This study reveals how Klotho and heparan sulfate glycosaminoglycan coreceptors enable FGF hormones to induce asymmetric 1:2 FGF–FGFR dimerization mandatory for FGFR kinase activation and hence signalling.

    • Lingfeng Chen
    • , Lili Fu
    •  & Moosa Mohammadi

  • Article |

    A new specific, small-molecule activator of the PI3Kα isoform (UCL-TRO-1938) identified through high-throughput screening can transiently activate PI3K signalling and biological responses in cells and tissues, with potential therapeutic applications in tissue protection and regeneration.

    • Grace Q. Gong
    • , Benoit Bilanges
    •  & Bart Vanhaesebroeck

  • Article
    | Open Access

    Analysis of the kinase activity of 300 protein Ser/Thr kinases reveals that the substrate specificity of the kinome is substantially more diverse than expected and is driven extensively by negative selectivity

    • Jared L. Johnson
    • , Tomer M. Yaron
    •  & Lewis C. Cantley

  • Article |

    β2-adrenergic receptor(β2AR) signalling induces ERK activity at endosomes, but not at the plasma membrane, and this activity is dependent on active, endosome-localized Gαs and requires ligand-stimulated β2AR endocytosis.

    • Yonghoon Kwon
    • , Sohum Mehta
    •  & Jin Zhang

  • Article |

    CDK11 associates with SF3B1 and phosphorylates threonine residues at the N terminus of SF3B1 during spliceosome activation, and the inhibition of CDK11 blocks the activation and leads to widespread intron retention and the accumulation of non-functional spliceosomes on pre-mRNAs and chromatin.

    • Milan Hluchý
    • , Pavla Gajdušková
    •  & Dalibor Blazek

  • Article
    | Open Access

    Reconstitution of the SARS-CoV-2 RNA 5′ cap reveals the unconventional mechanism by which SARS-CoV-2 caps its RNA genome, providing a new target in the development of antiviral agents to treat COVID-19.

    • Gina J. Park
    • , Adam Osinski
    •  & Vincent S. Tagliabracci

  • Article
    | Open Access

    The core cell cycle is largely driven by increasing total CDK activity together with minor differences in the substrate specificity of the CDKs initiating DNA replication and mitosis.

    • Souradeep Basu
    • , Jessica Greenwood
    •  & Paul Nurse

  • Article |

    Combining NMR spectroscopy-derived pseudocontact shifts (PCSs) with Carr–Purcell–Meiboom–Gill (CPMG) relaxation dispersion enables protein structure determination of lowly populated high-energy states that are essential for macromolecular function.

    • John B. Stiller
    • , Renee Otten
    •  & Dorothee Kern

  • Article |

    Unphosphorylated PINK1 of Pediculus humanus corporis forms a dimerized state before undergoing trans-autophosphorylation, and phosphorylated PINK1 undergoes a conformational change in the N-lobe to produce its phosphorylated, ubiquitin-binding state.

    • Zhong Yan Gan
    • , Sylvie Callegari
    •  & David Komander

  • Article |

    Cryo-electron microscopy, nuclear magnetic resonance and X-ray crystallography are used to provide structural and mechanistic details of the activation of anaplastic lymphoma kinase by the ligands ALKAL1 and ALKAL2.

    • Andrey V. Reshetnyak
    • , Paolo Rossi
    •  & Charalampos G. Kalodimos

  • Article |

    MARK4 regulates cardiomyocyte contractility by promoting MAP4 phosphorylation, which facilitates the access of VASH2 to microtubules for the detyrosination of α-tubulin; MARK4 deficiency after acute myocardial infarction limits the reduction in the left ventricular ejection fraction.

    • Xian Yu
    • , Xiao Chen
    •  & Xuan Li

  • Article |

    Crystal structures of the MEK kinase bound to the scaffold protein KSR and various MEK inhibitors, including the anti-cancer drug trametinib, reveal the molecular and functional mechanisms behind MEK inhibition.

    • Zaigham M. Khan
    • , Alexander M. Real
    •  & Arvin C. Dar

  • Article |

    The detection of microorganism-associated ligands by plant cells activates a signalling cascade in which the kinase BIK1 is monoubiquinated, released from the FLS2–BAK1 complex, and internalized by endocytosis.

    • Xiyu Ma
    • , Lucas A. N. Claus
    •  & Libo Shan

  • Article |

    Phosphorylation of INSIG1 and INSIG2 by PCK1 leads to a reduction in the binding of sterols, the activation of SREBP1 and SREBP2 and the downstream transcription of lipogenesis-associated genes that promote tumour growth.

    • Daqian Xu
    • , Zheng Wang
    •  & Zhimin Lu

  • Letter |

    The stress-activated kinase p38γ has a role in regulating entry into the cell cycle; in the liver, it can induce cellular proliferation during regeneration and promote the development of hepatocellular carcinoma.

    • Antonia Tomás-Loba
    • , Elisa Manieri
    •  & Guadalupe Sabio

  • Letter |

    The plant receptor kinase co-receptor BAK1 contains phosphosites that are required for immune function but not for brassinosteroid-regulated growth in Arabidopsis thaliana; an additional tyrosine phosphosite may be required for the function of many Arabidopsis receptor kinases.

    • Artemis Perraki
    • , Thomas A. DeFalco
    •  & Cyril Zipfel

  • Article |

    The cryo-electron microscopy and crystal structures of several mTORC1 complexes, and accompanying biochemical analyses, shed light on how mTORC1 is regulated and how cancer mutations lead to its hyperactivation.

    • Haijuan Yang
    • , Xiaolu Jiang
    •  & Nikola P. Pavletich

  • Letter |

    In budding yeast, glucose withdrawal, via the Rag GTPases, leads to TORC1 inhibition through its re-organization into a giant, vacuole-associated helix named a TOROID (TORC1 organized in inhibited domain).

    • Manoël Prouteau
    • , Ambroise Desfosses
    •  & Robbie Loewith

  • Letter |

    An allosteric inhibitor, EAI045, is reported that is selective for certain drug-resistant EGFR mutants, but spares the wild-type receptor; combination therapy of EAI045 with EGFR-dimerization-blocking antibodies is effective in mouse models of lung cancer driven by mutant versions of EGFR that are resistant to all previously developed inhibitors.

    • Yong Jia
    • , Cai-Hong Yun
    •  & Michael J. Eck

  • Letter |

    The mechanism of action of three different allosteric MEK inhibitors that target the MAP kinase pathway is investigated, and their efficacy is shown to be explained by the distinct mechanisms regulating MEK activation in KRAS- versus BRAF-driven tumours; this work provides a rationale for designing more effective cancer therapies for these common genetic subtypes of cancer.

    • Georgia Hatzivassiliou
    • , Jacob R. Haling
    •  & Marcia Belvin

  • Article |

    KAT5 tyrosine phosphorylation, mediated by the tyrosine kinase c-Abl, increases after DNA damage, promoting KAT5 binding to histone H3K9me3, which triggers KAT5-mediated acetylation of the ATM kinase; this promotes the activation of the DNA damage checkpoint and cell survival.

    • Abderrahmane Kaidi
    •  & Stephen P. Jackson

  • Letter |

    This study presents the crystal structures of three functional forms of diacylglycerol kinase, an integral membrane protein that catalyses a crucial step in oligosaccharide and lipopolysaccharide synthesis and assembly; these X-ray structures are markedly different from the only other structure available for this unique kinase that was solved using solution NMR.

    • Dianfan Li
    • , Joseph A. Lyons
    •  & Martin Caffrey

  • Article |

    Co-crystal structures of a number of complexes involving truncated mammalian target of rapamycin, a phosphoinositide 3-kinase-related protein kinase, reveal an intrinsically active kinase conformation and show how rapamycin–FKBP12 directly blocks substrate recruitment to the kinase domain.

    • Haijuan Yang
    • , Derek G. Rudge
    •  & Nikola P. Pavletich

  • News & Views |

    The orchestration of cell division requires a programme of events choreographed by protein modification. A study shows that the relative activity of a phosphatase enzyme towards its substrates imposes order during the final act of division.

    • Curt Wittenberg

  • Letter |

    Haematopoietic stem cells (HSCs) are very sensitive to energetic and oxidative stress, and modulation of the balance between their quiescence and proliferation is needed to respond to metabolic stress while preserving HSCs' long-term regenerative capacity. Here, and in two accompanying studies, it is shown that the tumour suppressor Lkb1 has a crucial role in maintaining energy homeostasis in haematopoietic cells.

    • Boyi Gan
    • , Jian Hu
    •  & Ronald A. DePinho

  • Letter |

    Toxoplasma gondii is an opportunistic human pathogen that secretes organelles called micronemes during infection. This is important for parasite motility, host-cell invasion and egress. It is now shown that the secretion of micronemes is dependent on the T. gondii calcium-dependent protein kinase 1. This kinase is not found in the parasite's mammalian hosts, and might represent a valid drug target.

    • Sebastian Lourido
    • , Joel Shuman
    •  & L. David Sibley

  • Letter |

    The amino-terminal tails of histone proteins are subject to a variety of post-translational modifications; addition or removal of these 'marks' facilitates gene activation or silencing. Here, a mechanism is defined that modulates the activity of the dual-specificity histone demethylase LSD1 during androgen-dependent transcription. Androgen-dependent signalling through protein kinase C beta I leads to phosphorylation of a histone amino acid, which prevents demethylation of an adjacent amino acid by LSD1.

    • Eric Metzger
    • , Axel Imhof
    •  & Roland Schüle

  • Letter |

    Plants and animals sense intruding pathogens by using proteins that recognize diverse microbe-associated molecular patterns (MAMPs) and initiate innate immune responses. Early signalling responses in the host include calcium influx, an oxidative burst and transcriptional reprogramming. Here, four calcium-dependent protein kinases are described that function as calcium sensors, act as convergence points for various MAMPs, and are crucial for transcriptional reprogramming and oxidative burst in plants.

    • Marie Boudsocq
    • , Matthew R. Willmann
    •  & Jen Sheen

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