Abiotic stress series Emerging MAP kinase pathways in plant stress signalling Hirofumi Nakagami, Andrea Pitzschke and Heribert Hirt Department of Genetics, Max F. Perutz Laboratories of the University of Vienna, Vienna Biocenter, Dr. Bohrgasse 9, A-1030 Vienna, Austria Mitogen-activated protein kinase (MAPK) pathways transfer information from sensors to cellular responses in all eukaryotes. A surprisingly large number of genes encoding MAPK pathway components have been uncovered by analysing model plant genomes, sug- gesting that MAPK cascades are abundant players of signal transduction. Recent investigations have con- firmed major roles of defined MAPK pathways in development, cell proliferation and hormone physi- ology, as well as in biotic and abiotic stress signalling. Latest insights and findings are discussed in the context of novel MAPK pathways in plant stress signalling. MAPK pathways – a common theme in eukaryotic signal transduction Humans, yeast and plants share w60% of their genes with each other, including components of conserved protein kinase signalling pathways. In all eukaryotes, mitogen- activated protein kinase (MAPK) pathways serve as highly conserved central regulators of growth, death, differentiation, proliferation and stress responses. A MAPK cascade minimally consists of a MAPKKK– MAPKK–MAPK module that is linked in various ways to upstream receptors and downstream targets. Receptor- mediated activation of a MAPKKK can occur through physical interaction and/or phosphorylation by either the receptor itself, intermediate bridging factors or interlink- ing MAPKKKKs. MAPKKKs are serine/threonine kinases that activate MAPKKs through phosphorylation on two serine/threonine residues in a conserved S/T–X 3–5 –S/T motif. By contrast, MAPKKs are dual-specificity kinases that phosphorylate MAPKs on threonine and tyrosine residues in the T–X–Y motif. MAPKs are promiscuous serine/ threonine kinases that phosphorylate a variety of substrates including transcription factors, protein kinases and cyto- skeleton-associated proteins. The specificity of different MAPK cascades functioning within the same cell is generated through the presence of docking domains found in various components of MAPK modules and scaffold proteins [1]. Components of plant MAPK cascades On the basis of the fully sequenced Arabidopsis genome, 20 MAPKs, 10 MAPKKs and 60 MAPKKKs were identified and a unified nomenclature for Arabidopsis MAPKs and MAPKKs was proposed [2]. By sequence comparison and signature motif searches, putative ortho- logues to most of the 20 MAPKs, 10 MAPKKs and 60 MAPKKKs can be identified in the available genomic or EST sequences of Medicago, tobacco and rice. However, in some cases, unequivocal definition of orthologues between different species is not possible, making a unified nomen- clature for all plant MAPKs, MAPKKs and MAPKKKs impossible at present. In all plant species, MAPKs carry either a TEY or TDY phosphorylation motif at the active site. In contrast to TEY MAPKs, all TDY MAPKs have long C-terminal extensions. To date, functional data for a TDY MAPK is only available for rice BWMK1 [3,4]. By contrast, the TEY MAPKs have been studied in many plant species, including Arabidopsis, Medicago, tobacco, tomato, parsley as well as rice (Table 1). Analysis of the putative MAPKKs reveals conservation of the N-terminal MAPK-docking motif K/R-K/R-K/R-X 1–6 - L-X-L/V/I, which, at least in Medicago SIMKK (stress- induced MAPKK), is required but not sufficient for MAPK activation [5]. Functional evidence for the role of MAPKKs is available for Arabidopsis MKK1, MKK2, MKK4, MKK5 and MKK6, Medicago PRKK and SIMKK, tobacco MEK1 and MEK2, tomato MKK2 and MKK4, parsley MKK5 and rice MEK1 (Table 1). Although the family of MAPKKKs forms the largest and most heterogeneous group of MAPK pathway components, it has only been shown in a few cases that these kinases do function as the activator of a MAPKK. Therefore, the classification of the 60–80 Arabidopsis kinases as MAPKKKs must be considered with caution. Nonetheless, these kinases are all related to each other and can be divided into two large subgroups: those of the MEKK-type, for which proof of MAPKKK function has been provided in most cases, and those of the Raf-like kinases, for which evidence that they act as MAPKKKs is still lacking. The MEKK-like kinases include Medicago OMTK1, Arabidopsis ANP1, ANP2, ANP3, MEKK1 and YODA and tobacco NPK1 (Table 1). Data on the Raf-like protein kinases include those for Arabidopsis CTR1 and EDR1 (Table 1). Because of space limitations, only recent literature on stress signalling MAPK pathways is discussed. Reviews on the basic composition and function of MAPK pathways in animals, yeast and plants are available [6–8]. Corresponding author: Hirt, H. (heribert.hirt@univie.ac.at). Available online 13 June 2005 Review TRENDS in Plant Science Vol.10 No.7 July 2005 www.sciencedirect.com 1360-1385/$ - see front matter Q 2005 Elsevier Ltd. All rights reserved. doi:10.1016/j.tplants.2005.05.009