EDR1 physically interacts with MKK4/MKK5 and negatively regulates a MAP kinase cascade to modulate plant innate immunity

PLoS Genet. 2014 May 15;10(5):e1004389. doi: 10.1371/journal.pgen.1004389. eCollection 2014.


Mitogen-activated protein (MAP) kinase signaling cascades play important roles in the regulation of plant defense. The Raf-like MAP kinase kinase kinase (MAPKKK) EDR1 negatively regulates plant defense responses and cell death. However, how EDR1 functions, and whether it affects the regulation of MAPK cascades, are not well understood. Here, we showed that EDR1 negatively regulates the MKK4/MKK5-MPK3/MPK6 kinase cascade in Arabidopsis. We found that edr1 mutants have highly activated MPK3/MPK6 kinase activity and higher levels of MPK3/MPK6 proteins than wild type. EDR1 physically interacts with MKK4 and MKK5, and this interaction requires the N-terminal domain of EDR1. EDR1 also negatively affects MKK4/MKK5 protein levels. In addition, the mpk3, mkk4 and mkk5 mutations suppress edr1-mediated resistance, and over-expression of MKK4 or MKK5 causes edr1-like resistance and mildew-induced cell death. Taken together, our data indicate that EDR1 physically associates with MKK4/MKK5 and negatively regulates the MAPK cascade to fine-tune plant innate immunity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Arabidopsis
  • Arabidopsis Proteins / immunology
  • Arabidopsis Proteins / metabolism*
  • Gene Expression Regulation, Plant
  • MAP Kinase Signaling System / genetics
  • Mitogen-Activated Protein Kinase Kinases / immunology
  • Mitogen-Activated Protein Kinase Kinases / metabolism*
  • Phosphorylation
  • Plant Diseases / genetics
  • Plant Diseases / immunology
  • Plant Immunity / genetics*
  • Plants, Genetically Modified / genetics


  • Arabidopsis Proteins
  • EDR1 protein, Arabidopsis
  • MKK4 protein, Arabidopsis
  • MKK5 protein, Arabidopsis
  • Mitogen-Activated Protein Kinase Kinases

Grant support

This work was supported by grants from the Strategic Priority Research Program of the Chinese Academy of Sciences (XDB11020100) (http://english.cas.cn/), National Basic Research Program of China (2011CB100700) (http://www.most.gov.cn/eng/), the National Transgenic Program of China (2011ZX08009-003) (http://english.agri.gov.cn/), the National Natural Science Foundation of China (31171160) (http://www.nsfc.gov.cn/Portal0/default166.htm) to DT, and the National Science Foundation (IOB-04541201) (http://www.nsf.gov/) to WL. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.