Signal Transduction
- GTPase ROP2 binds and promotes activation of target of rapamycin, TOR, in response to auxin
- Mikhail Schepetilnikov1,
- Joelle Makarian1,
- Ola Srour1,
- Angèle Geldreich1,
- Zhenbiao Yang2,
- Johana Chicher3,
- Philippe Hammann3 and
- Lyubov A Ryabova (lyuba.ryabova{at}ibmp-cnrs.unistra.fr)*,1
- 1Institut de Biologie Moléculaire des Plantes, Centre National de la Recherche Scientifique, UPR 2357, Université de Strasbourg, Strasbourg, France
- 2Department of Botany and Plant Sciences, Center for Plant Cell Biology, University of California, Riverside, CA, USA
- 3Plateforme Proteómique Strasbourg‐Esplanade, Centre National de la Recherche Scientifique, FRC 1589, Université de Strasbourg, Strasbourg, France
- ↵*Corresponding author. Tel: +33 3 67 15 53 31; Fax: +33 3 67 15 53 00; E‐mail: lyuba.ryabova{at}ibmp-cnrs.unistra.fr
Auxin signaling activates the small GTPase ROP2, causing TOR activation and increased translation of uORF‐containing mRNAs, thus making ROP2 the intervening link between auxin signaling and TOR‐dependent translation control.
Synopsis
Small GTPase ROP2 is a new component of the auxin‐responsive TOR signaling pathway, in which ROP2 activated by auxin promotes TOR activation and up‐regulation of translation of mRNAs that harbor uORFs within their leaders.
Small GTPase ROP2 interacts with TOR in Arabidopsis.
TOR is phosphorylated and activated in response to auxin via GTP‐bound ROP2.
ROP2 promotes TOR accumulation on endosome‐like structures.
GTP‐bound ROP2 promotes both polysome loading and translation reinitiation of mRNAs that harbor uORFs within their leaders in a TOR‐responsive manner.
The EMBO Journal (2017) 36: 886–903
- Received May 19, 2016.
- Revision received January 18, 2017.
- Accepted January 27, 2017.
- © 2017 The Authors
- ZRF1 is a novel S6 kinase substrate that drives the senescence programme
- Manuela Barilari1,2,3,†,
- Gregory Bonfils1,2,3,†,
- Caroline Treins1,2,3,†,
- Vonda Koka1,2,3,
- Delphine De Villeneuve1,2,3,
- Sylvie Fabrega4 and
- Mario Pende (mario.pende{at}inserm.fr)*,1,2,3
- 1Institut Necker‐Enfants Malades, Paris, France
- 2Inserm, U1151, Paris, France
- 3Université Paris Descartes, Sorbonne Paris Cité, Paris, France
- 4Plateforme Vecteurs Viraux et Transfert de Gènes, IFR94, Hôpital Necker Enfants‐Malades, Paris, France
- ↵*Corresponding author. Tel: +33 1 72 60 63 86; Fax: +33 1 72 60 64 01; E‐mail: mario.pende{at}inserm.fr
↵† These authors contributed equally to this work
Aberrant mTORC1 signalling induces cell senescence via S6 kinase‐mediated phosphorylation of epigenetic factor ZRF1, thereby linking nutritional cues to regulation of cell fitness.
Synopsis
Aberrant mTORC1 signalling induces cell senescence via S6 kinase‐mediated phosphorylation of epigenetic factor ZRF1, thereby linking nutritional cues to regulation of cell fitness.
S6 kinases are required for the senescence programme triggered by constitutive mTORC1 activation.
S6 kinases selectively regulate the p16 cell cycle inhibitor, without affecting the p53/p21‐dependent response.
A chemical genetic screen uncovers the epigenetic factor ZRF1 as a novel S6 kinase substrate, whose phosphorylation is triggered by nutritional cues and mTORC1 activity.
ZRF1 phosphorylation by S6 kinases participates in the senescence response.
The EMBO Journal (2017) 36: 736–750
- Received June 7, 2016.
- Revision received January 20, 2017.
- Accepted January 23, 2017.
- © 2017 The Authors. Published under the terms of the CC BY 4.0 license
This is an open access article under the terms of the Creative Commons Attribution 4.0 License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
- Balancing signals in the intestinal niche
During intestinal regeneration, opposing gradients of Wnt and BMP signaling ensure successful differentiation along the crypt/villus axis. In this issue of The EMBO Journal, Horiguchi et al (2017) show how intestinal subepithelial myofibroblasts can influence cell fate decisions in the regenerating intestine via autocrine secretion of angiopoietin‐like protein 2 (ANGPTL2).
See also: H Horiguchi et al (February 2017)
To ensure correct cell fate decisions during gut regeneration, intestinal subepithelial myofibroblasts regulate opposing gradients of Wnt and BMP signaling in the crypts via ANGPTL2 secretion.
- © 2017 The Authors. Published under the terms of the CC BY 4.0 license
This is an open access article under the terms of the Creative Commons Attribution 4.0 License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
- Cell signaling as a cognitive process
- Aneta Koseska (aneta.koseska{at}mpi-dortmund.mpg.de)*,1 and
- Philippe IH Bastiaens (philippe.bastiaens{at}mpi-dortmund.mpg.de)*,1,2
- 1Department of Systemic Cell Biology, Max Planck Institute of Molecular Physiology, Dortmund, Germany
- 2Faculty of Chemistry and Chemical Biology, TU Dortmund, Dortmund, Germany
- ↵*
Corresponding author. Tel: +49 231 133 2252; E‐mail: aneta.koseska{at}mpi-dortmund.mpg.de
Corresponding author. Tel: +49 231 133 2200; E‐mail: philippe.bastiaens{at}mpi-dortmund.mpg.de
This review discusses concepts for establishment of cellular heterogeneity in tissues, and proposes that cell identity is dynamically maintained in a cognitive manner, rather than intrinsically predetermined.
The EMBO Journal (2017) 36: 568–582
- Received August 1, 2016.
- Revision received October 13, 2016.
- Accepted December 20, 2016.
- © 2017 The Authors
- Nutrient sensing and TOR signaling in yeast and mammals
- ↵*Corresponding author. Tel: +41 61 207 21 50; E‐mail: m.hall{at}unibas.ch
As part of our metabolism focus, this review summarizes how nutrient availability is recognized and integrated by the conserved TOR cell growth regulator.
The EMBO Journal (2017) 36: 397–408
- Received November 3, 2016.
- Revision received December 12, 2016.
- Accepted December 15, 2016.
- © 2017 The Authors
- Discrete cytosolic macromolecular BRAF complexes exhibit distinct activities and composition
- Britta Diedrich1,2,†,
- Kristoffer TG Rigbolt1,2,10,†,
- Michael Röring3,†,
- Ricarda Herr3,
- Stephanie Kaeser‐Pebernard4,
- Christine Gretzmeier1,2,5,
- Robert F Murphy5,6,
- Tilman Brummer (tilman.brummer{at}zbsa.uni-freiburg.de)*,2,3,7,8,9,‡ and
- Jörn Dengjel (joern.dengjel{at}unifr.ch)*,1,2,4,5,7,‡
- 1Department of Dermatology, Medical Center ‐ University of Freiburg, Freiburg, Germany
- 2ZBSA Center for Biological Systems Analysis, University of Freiburg, Freiburg, Germany
- 3Faculty of Medicine, Institute of Molecular Medicine and Cell Research (IMMZ), University of Freiburg, Freiburg, Germany
- 4Department of Biology, University of Fribourg, Fribourg, Switzerland
- 5Freiburg Institute for Advanced Studies (FRIAS), University of Freiburg, Freiburg, Germany
- 6Computational Biology Department and Department of Biomedical Engineering, Carnegie Mellon University, Pittsburgh, PA, USA
- 7Centre for Biological Signalling Studies BIOSS, University of Freiburg, Freiburg, Germany
- 8Comprehensive Cancer Centre, Freiburg, Germany
- 9German Cancer Consortium (DKTK), partner site Freiburg, and German Cancer Research Center (DKFZ), Heidelberg, Germany
- 10Gubra, Hørsholm, Denmark
- ↵*
Corresponding author. Tel: +49 761 2039610; E‐mail: tilman.brummer{at}zbsa.uni-freiburg.de
Corresponding author. Tel: +41 26 300 8631; E‐mail: joern.dengjel{at}unifr.ch
Proteomics‐based identification of distinct molecular interactions and modifications of wild‐type and melanoma‐associated mutant BRAF reveals the effects of BRAF activators and inhibitors on the quaternary structure of this major therapeutic target.
Synopsis
The serine/threonine kinase BRAF plays a key role in development and homeostasis and represents the most frequently mutated kinase in tumors. We characterize two macromolecular, cytosolic BRAF complexes of distinct molecular composition and phosphorylation status.
BRAF resides minimally in two distinct macromolecular cytosolic protein complexes.
Active BRAF forms larger complexes characterized by the presence of HSP90/CDC37.
Less active BRAF resides in smaller complexes characterized by 14‐3‐3 proteins.
Clinically relevant kinase inhibitors alter BRAF complex compositions depending on the expressed BRAF mutant.
The EMBO Journal (2017) 36: 646–663
- Received May 10, 2016.
- Revision received December 6, 2016.
- Accepted December 9, 2016.
- © 2017 The Authors
- ANGPTL2 expression in the intestinal stem cell niche controls epithelial regeneration and homeostasis
- Haruki Horiguchi (horiguti{at}kumamoto-u.ac.jp)*,1,2,
- Motoyoshi Endo (enmoto{at}gpo.kumamoto-u.ac.jp)*,1,
- Kohki Kawane3,
- Tsuyoshi Kadomatsu1,
- Kazutoyo Terada1,
- Jun Morinaga1,
- Kimi Araki2,
- Keishi Miyata1 and
- Yuichi Oike (oike{at}gpo.kumamoto-u.ac.jp)*,1
- 1Department of Molecular Genetics, Graduate School of Medical sciences, Kumamoto University, Chuo‐ku Kumamoto, Japan
- 2Institute of Resource Development and Analysis, Kumamoto University, Chuo‐ku Kumamoto, Japan
- 3Faculty of Life Sciences, Kyoto Sangyo University, Kita‐ku Kyoto, Japan
- ↵*
Corresponding author. Tel: +81 96 373 5140; Fax: +81 96 373 5145; E‐mail: horiguti{at}kumamoto-u.ac.jp
Corresponding author. Tel: +81 96 373 5140; Fax: +81 96 373 5145; E‐mail: enmoto{at}gpo.kumamoto-u.ac.jp
Corresponding author. Tel: +81 96 373 5140; Fax: +81 96 373 5145; E‐mail: oike{at}gpo.kumamoto-u.ac.jp
ANGPTL2 is secreted upon intestinal injury and regulates the balance between β‐catenin and BMP signaling to promote intestinal stem cell maintenance and proliferation.
Synopsis
ANGPTL2 regulates stem cell activity and epithelial regeneration in the intestine. Intestinal subepithelial myofibroblasts secrete ANGPTL2 to maintain the intestinal stem cell niche by modulating proper BMP levels and β‐catenin signaling.
ANGPTL2 is required for regeneration of intestinal epithelium after injury.
ANGPTL2 is expressed in intestinal subepithelial myofibroblasts.
Autocrine ANGPTL2 downregulates Bmp expression via integrin α5β1/NF‐κB signaling.
Aberrant BMP signaling in Angptl2‐deficient mice decreases intestinal epithelial stem cell activity.
The EMBO Journal (2017) 36: 409–424
- Received September 9, 2016.
- Revision received November 30, 2016.
- Accepted November 30, 2016.
- © 2017 The Authors. Published under the terms of the CC BY 4.0 license
This is an open access article under the terms of the Creative Commons Attribution 4.0 License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
- MRTF potentiates TEAD‐YAP transcriptional activity causing metastasis
- Tackhoon Kim (tackhoon.k{at}kaist.ac.kr)*,1,†,
- Daehee Hwang1,†,
- Dahye Lee1,
- Jeong‐Hwan Kim2,
- Seon‐Young Kim2 and
- Dae‐Sik Lim (daesiklim{at}kaist.ac.kr)*,1
- 1National Creative Research Initiatives Center for Cell Division and Differentiation, Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, Korea
- 2Medical Genomics Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon, Korea
- ↵*
Corresponding author. Tel: +82 42 350 2675; E‐mail: tackhoon.k{at}kaist.ac.kr
Corresponding author. Tel: +82 42 350 2635; E‐mail: daesiklim{at}kaist.ac.kr
↵† These authors contributed equally to this work
Crosstalk with transcription factor MRTF enhances TEAD‐YAP oncogenic activity, coordinating signal transduction of extracellular GPCR ligands involved in cancer cell invasion or actin cytoskeletal disruption.
Synopsis
Oncogenic activity of TEAD‐YAP transcription complex is enhanced by MRTF proteins, which recruit NcoA3. MRTF–YAP interaction highlights a novel mode of signal transduction that regulates YAP activity independently of subcellular localization.
MRTF family proteins activate TEAD‐YAP by direct binding through PPXY–WW domain interaction.
MRTF–YAP interaction is required for TEAD‐YAP target gene expression and promotion of cancer cell invasion and metastasis.
MRTF binding to TEAD‐YAP recruits NcoA3 for full potentiation of TEAD‐YAP activity.
MRTF–YAP interaction constitutes a LATS‐independent regulatory mechanism on TEAD‐YAP activity.
The EMBO Journal (2017) 36: 520–535
- Received June 28, 2016.
- Revision received November 25, 2016.
- Accepted November 28, 2016.
- © 2016 The Authors
- Negative regulation of type I IFN signaling by phosphorylation of STAT2 on T387
- Yuxin Wang1,2,
- Jing Nan2,3,
- Belinda Willard4,
- Xin Wang5,
- Jinbo Yang (yangjb{at}ouc.edu.cn)*,1,3 and
- George R Stark (starkg{at}ccf.org)*,2
- 1Key Laboratory of Marine Drugs, Ministry of Education Ocean University of China, Qingdao, Shandong, China
- 2Department of Cancer Biology, Lerner Research Institute The Cleveland Clinic Foundation, Cleveland, OH, USA
- 3Institute of Cancer Biology & Drug Screening, School of Life Sciences Lanzhou University, Lanzhou, Gansu, China
- 4Proteomics and Metabolomics Laboratory, Lerner Research Institute The Cleveland Clinic Foundation, Cleveland, OH, USA
- 5Department of Immunology, Lerner Research Institute The Cleveland Clinic Foundation, Cleveland, OH, USA
- ↵*
Corresponding author. Tel: +1 216 444 6062; E‐mail: starkg{at}ccf.org
Corresponding author. Tel: +86 532 80932635; E‐mail: yangjb{at}ouc.edu.cn
Cyclin‐dependent kinase‐promoted phosphorylation of STAT2 at T387 inhibits type I IFN‐dependent signaling with effects on viral and cell proliferative responses.
Synopsis
An analysis by mass spectrometry revealed that the majority of STAT2 in cells is phosphorylated on T387 constitutively. This modification negatively regulates signaling responses to type I interferons. T387 lies in a consensus site for cyclin‐dependent kinases, suggesting that CDK inhibitors might augment responses to type I interferons.
STAT2 is phosphorylated on T387, which is located in the DNA‐binding domain.
STAT2 T387 phosphorylation negatively regulates type I IFN signaling.
The glucocorticoid signaling pathway affects T387 phosphorylation.
CDK inhibitors downregulate STAT2 T387 phosphorylation.
The EMBO Journal (2017) 36: 202–212
- Received May 23, 2016.
- Revision received October 6, 2016.
- Accepted October 11, 2016.
- © 2016 The Authors
- The Arabidopsis CERK1‐associated kinase PBL27 connects chitin perception to MAPK activation
- Kenta Yamada1,†,
- Koji Yamaguchi1,†,
- Tomomi Shirakawa1,
- Hirofumi Nakagami2,‡,
- Akira Mine3,4,‡,
- Kazuya Ishikawa1,
- Masayuki Fujiwara5,
- Mari Narusaka6,
- Yoshihiro Narusaka6,
- Kazuya Ichimura2,7,
- Yuka Kobayashi1,
- Hidenori Matsui2,
- Yuko Nomura2,
- Mika Nomoto4,
- Yasuomi Tada4,
- Yoichiro Fukao8,
- Tamo Fukamizo1,
- Kenichi Tsuda3,
- Ken Shirasu2,
- Naoto Shibuya9 and
- Tsutomu Kawasaki (t-kawasaki{at}nara.kindai.ac.jp)*,1
- 1Department of Advanced Bioscience, Graduate School of Agriculture, Kindai University, Nakamachi Nara, Japan
- 2RIKEN Center for Sustainable Resource Science, Tsurumi‐ku Yokohama, Japan
- 3Department of Plant Microbe Interactions, Max Planck Institute for Plant Breeding Research, Cologne, Germany
- 4Center for Gene Research, Nagoya University, Chikusa‐Ku Nagoya, Japan
- 5Institute for Advanced Biosciences, Keio University, Tsuruoka Yamagata, Japan
- 6Research Institute for Biological Sciences Okayama, Kaga‐gun Okayama, Japan
- 7Faculty of Agriculture, Kagawa University, Miki‐cho Kita‐gun Kagawa, Japan
- 8Department of Bioinformatics, Ritsumeikan University, Kusatsu Shiga, Japan
- 9Department of Life Sciences, School of Agriculture, Meiji University, Tama‐ku Kawasaki Kanagawa, Japan
- ↵*Corresponding author. Tel: +81 742 43 7335; E‐mail: t-kawasaki{at}nara.kindai.ac.jp
Chitin receptor CERK1 transmits immune signals to the intracellular MAPK cascade in plants. This occurs via phosphorylation of MAPKKK5 by the CERK1‐associated kinase PBL27, providing a missing link between pathogen perception and signaling output.
Synopsis
Chitin receptor CERK1 transmits immune signals to the intracellular MAPK cascade in plants. This occurs via phosphorylation of MAPKKK5 by the CERK1‐associated kinase PBL27, providing a missing link between pathogen perception and signaling output.
CERK1‐associated kinase PBL27 interacts with MAPKKK5 at the plasma membrane.
Chitin perception induces disassociation of PBL27 and MAPKKK5.
PBL27 functions as a MAPKKK kinase.
Phosphorylation of MAPKKK5 by PBL27 is enhanced upon phosphorylation of PBL27 by CERK1.
Phosphorylation of MAPKKK5 by PBL27 is required for chitin‐induced MAPK activation in planta.
The EMBO Journal (2016) 35: 2468–2483
- Received March 3, 2016.
- Revision received August 26, 2016.
- Accepted August 30, 2016.
- © 2016 The Authors. Published under the terms of the CC BY NC ND 4.0 license
This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial‐NoDerivs 4.0 License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.
Pages
