title: Attenuation of pattern recognition receptor signaling is mediated by a MAP kinase kinase kinase.
abstract: Pattern recognition receptors (PRRs) play a key role in plant and animal innate immunity. PRR binding of their cognate ligand triggers a signaling network and activates an immune response. Activation of PRR signaling must be controlled prior to ligand binding to prevent spurious signaling and immune activation. Flagellin perception in Arabidopsis through FLAGELLIN-SENSITIVE 2 (FLS2) induces the activation of mitogen-activated protein kinases (MAPKs) and immunity. However, the precise molecular mechanism that connects activated FLS2 to downstream MAPK cascades remains unknown. Here, we report the identification of a differentially phosphorylated MAP kinase kinase kinase that also interacts with FLS2. Using targeted proteomics and functional analysis, we show that MKKK7 negatively regulates flagellin-triggered signaling and basal immunity and this requires phosphorylation of MKKK7 on specific serine residues. MKKK7 attenuates MPK6 activity and defense gene expression. Moreover, MKKK7 suppresses the reactive oxygen species burst downstream of FLS2, suggesting that MKKK7-mediated attenuation of FLS2 signaling occurs through direct modulation of the FLS2 complex.
authors.affiliation: Department of Biology, Faculty of Science, Utrecht University, Utrecht, The Netherlands.
authors.forename: Sharon C
authors.initials: SC
authors.lastname: Mithoe
authors.affiliation: Department of Biology, Institute of Molecular Systems Biology, ETH Zürich, Zürich, Switzerland.
authors.forename: Christina
authors.initials: C
authors.lastname: Ludwig
authors.affiliation: Department of Biology, Faculty of Science, Utrecht University, Utrecht, The Netherlands.
authors.forename: Michiel J C
authors.initials: MJ
authors.lastname: Pel
authors.affiliation: Department of Biology, Faculty of Science, Utrecht University, Utrecht, The Netherlands.
authors.forename: Mara
authors.initials: M
authors.lastname: Cucinotta
authors.affiliation: Department of Biology, Faculty of Science, Utrecht University, Utrecht, The Netherlands.
authors.forename: Alberto
authors.initials: A
authors.lastname: Casartelli
authors.affiliation: The Sainsbury Laboratory, Norwich Research Park, Norwich, UK.
authors.forename: Malick
authors.initials: M
authors.lastname: Mbengue
authors.affiliation: The Sainsbury Laboratory, Norwich Research Park, Norwich, UK.
authors.forename: Jan
authors.initials: J
authors.lastname: Sklenar
authors.affiliation: The Sainsbury Laboratory, Norwich Research Park, Norwich, UK.
authors.forename: Paul
authors.initials: P
authors.lastname: Derbyshire
authors.affiliation: The Sainsbury Laboratory, Norwich Research Park, Norwich, UK.
authors.forename: Silke
authors.initials: S
authors.lastname: Robatzek
authors.affiliation: Department of Biology, Faculty of Science, Utrecht University, Utrecht, The Netherlands.
authors.forename: Corné M J
authors.initials: CM
authors.lastname: Pieterse
authors.affiliation: Department of Biology, Institute of Molecular Systems Biology, ETH Zürich, Zürich, Switzerland Faculty of Science, University of Zürich, Zürich, Switzerland.
authors.forename: Ruedi
authors.initials: R
authors.lastname: Aebersold
authors.affiliation: Department of Biology, Faculty of Science, Utrecht University, Utrecht, The Netherlands The Sainsbury Laboratory, Norwich Research Park, Norwich, UK frank.menke@tsl.ac.uk.
authors.forename: Frank L H
authors.initials: FL
authors.lastname: Menke
mesh_terms: D017360:Arabidopsis / Q000235:genetics / Q000378:metabolism*; D029681:Arabidopsis Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D005408:Flagellin / Q000378:metabolism; D020935:MAP Kinase Signaling System; D020929:Mitogen-Activated Protein Kinase Kinases / Q000235:genetics / Q000378:metabolism*; D020928:Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism*; D057865:Plant Immunity; D011485:Protein Binding; D011494:Protein Kinases / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D029681:Arabidopsis Proteins; D017382:Reactive Oxygen Species; D005408:Flagellin; D011494:Protein Kinases; C411853:FLS2 protein, Arabidopsis; C436293:MPK6 protein, Arabidopsis; D020928:Mitogen-Activated Protein Kinases; D020929:Mitogen-Activated Protein Kinase Kinases
keywords: Arabidopsis; innate immunity; phosphorylation; signaling; targeted proteomics