Intracellular signalling peptides and proteins articles within Nature Communications

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  • Article
    | Open Access

    The molecular basis for the functional versatility of β-arrestins in the G-protein coupled receptor signaling pathway is not well understood. Here, the authors use19F NMR spectroscopy to show that different binding partners activate β-arrestin-1 through distinct mechanisms.

    • Ruibo Zhai
    • , Zhuoqi Wang
    •  & Yunfei Hu

  • Article
    | Open Access

    MAVS is an adapter protein involved in RIG-I-like receptor (RLR) signaling. Here, the authors show how MAVS link RLR-mediated signaling and glucose metabolism, employing distinct mechanisms in different organelles.

    • Qiao-qiao He
    • , Yu Huang
    •  & Shi Liu

  • Article
    | Open Access

    Glycogen metabolism is tightly regulated. Here the authors describe the 3D structure of the PP1/PTG protein complex, which plays a prominent role in the activation of glycogen synthesis and in the pathogenesis of Lafora disease, the most severe form of pediatric progressive epilepsy.

    • Marta Stefania Semrau
    • , Gabriele Giachin
    •  & Graziano Lolli

  • Article
    | Open Access

    Rep15 is an effector that interacts with the GTPase Rab15. Here, the authors show that Rep15 also interacts with Rab3 paralogs and Rab34, present crystal structures of Rep15:Rab complexes and find that Rep15 depletion in glioblastoma cells decreases proliferation and mobility.

    • Amrita Rai
    • , Anurag K. Singh
    •  & Roger S. Goody

  • Article
    | Open Access

    Notch signalling is reported to be hyperactivated in oestrogen receptor-negative (ER-) breast cancer. Here the authors show that G protein-coupled receptor kinase-interacting protein 1 (GIT1) negatively regulates Notch signalling and tumour growth in ER- breast cancer by blocking Notch ICD nuclear translocation.

    • Songbai Zhang
    • , Ayako Miyakawa
    •  & Per Uhlén

  • Article
    | Open Access

    Nuclear translocation of the p50/p65 heterodimer is essential for NF-κB signaling. Here, the authors identify a bipartite Nuclear Localization Signal in the NF-κB p50/p65 heterodimer that is recognized with high affinity by importin α3.

    • Tyler J. Florio
    • , Ravi K. Lokareddy
    •  & Gino Cingolani

  • Article
    | Open Access

    GPCR kinases (GRKs) phosphorylate active-form G-protein-coupled receptors (GPCRs). Here, the authors reveal that Gq heterotrimer coupled with the angiotensin II type-1 receptor (AT1R) determines the GRK subtypes recruited to the complex in a microdomain, thus defining subsequent AT1R phosphorylation patterns, β-arrestin conformation and functionality.

    • Kouki Kawakami
    • , Masataka Yanagawa
    •  & Asuka Inoue

  • Article
    | Open Access

    14-3-3 proteins recognize phosphorylated motifs within numerous protein partners. Here, the authors characterize the binding of all human 14-3-3 isoforms to four E6 oncoproteins, and identify a fixed order of 14-3-3 binding affinities that is conserved in 14-3-3:phosphoprotein interactions across the proteome.

    • Gergo Gogl
    • , Kristina V. Tugaeva
    •  & Nikolai N. Sluchanko

  • Article
    | Open Access

    The low-density lipoprotein receptor-related protein 6 (LRP6) is a co-receptor of the β-catenin-dependent Wnt signaling pathway and interacts with the Wnt inhibitor sclerostin (SOST). Here the authors present the crystal structure of SOST in complex with the LRP6 E1E2 ectodomain construct, which reveals that the SOST C-terminus binds to the LRP6 E2 domain, and further validate this binding site with in vitro and in vivo experiments.

    • Jinuk Kim
    • , Wonhee Han
    •  & Hee-Jung Choi

  • Article
    | Open Access

    Optogenetic manipulation of protein localisation in cells involves the creation of fusions that can influence activity. Here the authors develop a near-infrared light-responsive aptamer-based system to regulate the nuclear-cytoplasmic shuttling of NF-κB subunit RelA.

    • Sitao Xie
    • , Yulin Du
    •  & Weihong Tan

  • 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

    Stromal interaction molecule 1 (STIM1) monitors ER-luminal Ca2+ levels to maintain cellular Ca2+ balance. Here the authors find that the STIM1 luminal domain monomer has multiple Ca2+ - binding sites which set the threshold for physiological activation of STIM1 in cells.

    • Aparna Gudlur
    • , Ana Eliza Zeraik
    •  & Patrick G. Hogan

  • Article
    | Open Access

    Protein phosphatase1 (PP1), a signalling and transcriptional regulator, and epigenetic modulator is known to be a memory suppressor. Here the authors show that memory control by PP1 involves the microRNA cluster miR-183/96/182, and that this cluster is selectively regulated during memory formation in mice.

    • Bisrat T. Woldemichael
    • , Ali Jawaid
    •  & Isabelle M. Mansuy

  • Article
    | Open Access

    Identifying pathways that cause pathological cardiac hypertrophy holds great therapeutic potential. Here the authors discover one such pathway and show that SIKE, an inhibitor of interferon signalling, prevents pathological but not physiological cardiac hypertrophy by interacting with TBK1 and modulating the TBK1/AKT signalling in rodents and monkeys.

    • Ke-Qiong Deng
    • , Aibing Wang
    •  & Hongliang Li

  • Article
    | Open Access

    It is unclear how the extracellular signal-regulated kinases 1 and 2 (ERK1/2) pathways interact with other signals in intestinal epithelial cells. Here, the authors show that upon loss of Erk1/2, or pharmacological inhibition of MEK1/2, the ERK5 pathway is upregulated to maintain epithelial cell proliferation.

    • Petrus R. de Jong
    • , Koji Taniguchi
    •  & Eyal Raz

  • Article
    | Open Access

    14-3-3 proteins regulate several signalling pathways but often act redundantly; however, the molecular mechanisms behind such redundancy are unclear. Here, the authors show that 14-3-3 proteins regulate two interacting components of Tor signalling in Drosophila, Tctp and Rheb, disrupting organ development.

    • Thao Phuong Le
    • , Linh Thuong Vuong
    •  & Kwang-Wook Choi

  • Article
    | Open Access

    Wnt/β-catenin signalling directs several developmental processes and is aberrantly activated in several cancers. Here the authors implicate Tankyrase—previously shown to target the scaffolding protein Axin for proteolysis—in early Wnt signalling by promoting the interaction between Axin and the Wnt co-receptor LRP6.

    • Eungi Yang
    • , Ofelia Tacchelly-Benites
    •  & Yashi Ahmed

  • Article
    | Open Access

    Centralspindlin consists of dimeric kinesin-6 and dimeric RacGAP, and is involved in the organization of anaphase midzone microtubules. Here, the authors show that the RacGAP is needed for motor activity at the plus-end of microtubules, but not for the bundling activity associated with kinesin-6.

    • Li Tao
    • , Barbara Fasulo
    •  & William Sullivan

  • Article
    | Open Access

    Ian Blair and colleagues use genome-wide linkage analysis and whole exome sequencing to identify mutations in the CCNF gene in large cohorts of amyotrophic lateral sclerosis and frontotemporal dementia patients. In addition to validating the mutations in international cohorts, the authors also show that mutant CCNFgene product affects ubiquitination and protein degradation in cultured cells.

    • Kelly L. Williams
    • , Simon Topp
    •  & Ian P. Blair

  • Article
    | Open Access

    The accumulation of senescent cells within tissues plays a role in numerous age-related pathologies. Yosef and Pilpel et al. demonstrate that the resistance of these cells to apoptosis is driven by upregulation of survival proteins, whose pharmacological inhibition triggers senescent cell elimination in mice.

    • Reut Yosef
    • , Noam Pilpel
    •  & Valery Krizhanovsky

  • Article
    | Open Access

    Calmodulin is an important calcium sensor that can recognise and interact with a large range of proteins. Here, the authors use molecular dynamics simulations and Markov state models to show that the range of binding conformations adopted without substrate can help explain its diverse and specific binding.

    • Diwakar Shukla
    • , Ariana Peck
    •  & Vijay S. Pande

  • Article
    | Open Access

    AMPK regulates the metabolism and so drugs that activate AMPK might have potential for the treatment of metabolic disease. Here, the authors report the structure of AMPK bound to an activating compound, revealing two binding sites and indicating that dual therapy might be a good drug strategy.

    • Christopher G. Langendorf
    • , Kevin R. W. Ngoei
    •  & Bruce E. Kemp

  • Article
    | Open Access

    High aldosterone levels cause heart damage independently of its well-known effect on blood pressure. Here, Cannavo et al. show that aldosterone-mediated cardiac pathology involves G protein-coupled receptor (GPCR) kinase 2 (GRK2) and GRK5 that integrate signals from angiotensin II receptor (AT1R).

    • Alessandro Cannavo
    • , Daniela Liccardo
    •  & Walter J. Koch

  • Article
    | Open Access

    The signal recognition particle plays a key role in the co-translational protein targeting of membrane and secretory proteins. Here the authors report a crystal structure of the ternary SRP complex in signal sequence bound and unbound forms, providing insight into how signal sequence binding is coupled to SRP receptor interaction.

    • Tobias Hainzl
    •  & A. Elisabeth Sauer-Eriksson

  • Article |

    The extracellular signal-regulated kinase 1/2 (ERK1/2) cascade is involved in the induction and maintenance of cancers. Here the authors design an ERK-derived peptide that blocks ERK nuclear import, thus proposing a novel approach to treat tumours with mutational activation of the ERK pathway.

    • Alexander Plotnikov
    • , Karen Flores
    •  & Rony Seger

  • Article |

    Pruning of newly formed blood vessels is an important and yet poorly understood aspect of angiogenesis. Here the authors show that endothelial phosphotyrosine-dependent EphrinB2 signalling represses JNK3 function via STAT1, and identify JNK3 as an effector of endothelial cell death and vessel pruning in mice.

    • Ombretta Salvucci
    • , Hidetaka Ohnuki
    •  & Giovanna Tosato

  • Article
    | Open Access

    Activation of the Met receptor by hepatocyte growth factor requires Met receptor dimerization. Here, the authors identify Met-binding peptide macrocycles that, in a dimeric form as a result of chemical crosslinking, induce Met receptor dimerization and activation in cultured human cells.

    • Kenichiro Ito
    • , Katsuya Sakai
    •  & Hiroaki Suga

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