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Attenuation of pattern recognition receptor signaling is mediated by a MAP kinase kinase kinase
Authors:Sharon C Mithoe  Christina Ludwig  Michiel JC Pel  Mara Cucinotta  Alberto Casartelli  Malick Mbengue  Jan Sklenar  Paul Derbyshire  Silke Robatzek  Corné MJ Pieterse  Ruedi Aebersold  Frank LH Menke
Affiliation:1. Department of Biology, Faculty of Science, Utrecht University, Utrecht, The Netherlands;2. Department of Biology, Institute of Molecular Systems Biology, ETH Zürich, Zürich, Switzerland;3. The Sainsbury Laboratory, Norwich Research Park, Norwich, UK;4. Faculty of Science, University of Zürich, Zürich, Switzerland
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.
Keywords:   Arabidopsis     innate immunity  phosphorylation  signaling  targeted proteomics
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