The MKK2 pathway mediates cold and salt stress signaling in Arabidopsis

Mol Cell. 2004 Jul 2;15(1):141-52. doi: 10.1016/j.molcel.2004.06.023.


The Arabidopsis mitogen-activated protein kinase (MAPK) kinase 2 (MKK2) and the downstream MAPKs MPK4 and MPK6 were isolated by functional complementation of osmosensitive yeast mutants. In Arabidopsis protoplasts, MKK2 was specifically activated by cold and salt stress and by the stress-induced MAPK kinase kinase MEKK1. Yeast two-hybrid, in vitro, and in vivo protein kinase assays revealed that MKK2 directly targets MPK4 and MPK6. Accordingly, plants overexpressing MKK2 exhibited constitutive MPK4 and MPK6 activity, constitutively upregulated expression of stress-induced marker genes, and increased freezing and salt tolerance. In contrast, mkk2 null plants were impaired in MPK4 and MPK6 activation and were hypersensitive to salt and cold stress. Full genome transcriptome analysis of MKK2-overexpressing plants demonstrated altered expression of 152 genes involved in transcriptional regulation, signal transduction, cellular defense, and stress metabolism. These data identify a MAP kinase signaling cascade mediating cold and salt stress tolerance in plants.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Arabidopsis / drug effects
  • Arabidopsis / enzymology
  • Arabidopsis / metabolism*
  • Arabidopsis Proteins / genetics
  • Arabidopsis Proteins / isolation & purification
  • Arabidopsis Proteins / metabolism*
  • Cold Temperature
  • Enzyme Activation / drug effects
  • Gene Expression Regulation, Plant / genetics
  • MAP Kinase Kinase Kinases / metabolism
  • MAP Kinase Signaling System / drug effects
  • MAP Kinase Signaling System / genetics*
  • Mitogen-Activated Protein Kinase Kinases / genetics
  • Mitogen-Activated Protein Kinase Kinases / isolation & purification
  • Mitogen-Activated Protein Kinase Kinases / metabolism*
  • Mitogen-Activated Protein Kinases / metabolism
  • Mutation / genetics
  • Phenotype
  • Saline Solution, Hypertonic / pharmacology
  • Up-Regulation / genetics
  • Yeasts / enzymology
  • Yeasts / genetics


  • Arabidopsis Proteins
  • Saline Solution, Hypertonic
  • AtMPK4 protein, Arabidopsis
  • MPK6 protein, Arabidopsis
  • Mitogen-Activated Protein Kinases
  • MAP Kinase Kinase Kinases
  • MKK2 protein, Arabidopsis
  • Mitogen-Activated Protein Kinase Kinases