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.

Receptor Kinases in Plant-Pathogen Interactions: More Than Pattern Recognition

“…However, it is not clear how MAPKKK5 activates MPK4, which is known to be activated by MEKK1, MKK1, and MKK2. Another MAPKKK, MAPKKK7, has been shown to interact with FLS2 to negatively regulate flg22-triggered MPK activation, but the underlying mechanism remains unknown (Mithoe et al, 2016). Moreover, a bacterial protease called PrpL was shown to trigger MPK activation potentially through an unknown PRR (Cheng et al, 2015).…”

From Chaos to Harmony: Responses and Signaling upon Microbial Pattern Recognition

“…Interestingly, in contrast to the compromised MPK3/MPK6 activation triggered by chitin, the mapkkk5 mutant shows elevated MPK3/MPK6 activation stimulated by flg22, suggesting that MAPKKK5 inversely regulates chitin- and flg22-triggered signaling (162). In contrast, the MAPKKK MKKK7, associated with FLS2 and phosphorylated upon flg22 treatment, negatively regulates flg22-triggered MPK6 activation and the ROS burst through unknown mechanisms (113). …”

Behind the lines–actions of bacterial type III effector proteins in plant cells

“…Recently, it was shown that FLS2-mediated PTI responses are also suppressed by the MAP kinase kinase kinase MKKK7, which interacts with FLS2 and is phosphorylated upon flg22 perception (Mithoe et al. 2016). …”