The Role of Serine-Threonine Protein Phosphatase PP2A in Plant Oxidative Stress Signaling-Facts and Hypotheses

Abstract

Abiotic and biotic factors induce oxidative stress involving the production and scavenging of reactive oxygen species (ROS). This review is a survey of well-known and possible roles of serine-threonine protein phosphatases in plant oxidative stress signaling, with special emphasis on PP2A. ROS mediated signaling involves three interrelated pathways: (i) perception of extracellular ROS triggers signal transduction pathways, leading to DNA damage and/or the production of antioxidants; (ii) external signals induce intracellular ROS generation that triggers the relevant signaling pathways and (iii) external signals mediate protein phosphorylation dependent signaling pathway(s), leading to the expression of ROS producing enzymes like NADPH oxidases. All pathways involve inactivation of serine-threonine protein phosphatases. The metal dependent phosphatase PP2C has a negative regulatory function during ABA mediated ROS signaling. PP2A is the most abundant protein phosphatase in eukaryotic cells. Inhibitors of PP2A exert a ROS inducing activity as well and we suggest that there is a direct relationship between these two effects of drugs. We present current findings and hypotheses regarding PP2A-ROS signaling connections related to all three ROS signaling pathways and anticipate future research directions for this field. These mechanisms have implications in the understanding of stress tolerance of vascular plants, having applications regarding crop improvement.

Keywords: PP2A; ROS signaling pathways; plant oxidative stress; protein phosphatase; reactive oxygen species.

Figure 1

ROS-related targets of PP2A inhibitors in plants. Clear lines/arrows show mechanisms that are already elucidated, while dashed lines/arrows show mechanisms for which some evidence exists, but further research is needed for clarifying. As can be seen, all inhibitors activate MAPK cascades by PP2A inhibition and this might be a key step in the production of ROS via RBOH. On the other hand, a decrease in reduced glutathione (GSH) pool due to the formation of GSH-MCY-LR (or cantharidin) conjugates leads to the elevation of ROS levels in a PP2A independent pathway. For MCY-LR, there are three possible mechanisms of oxidative stress induction (see text) of which mechanisms 1 and 3 that have been proven for plants are presented here. Lipid peroxidation and protein oxidation can originate from both mechanisms as shown in the Figure, thus a clear separation of these mechanisms is difficult. It was not our scope to show here the uptake mechanisms of inhibitors by plasma membrane and endomembranes. GSH: reduced glutathione; MCY-LR: microcystin-LR; CA: calyculin A; OA: okadaic acid. The effects of different inhibitors are shown as red: MCY-LR; green: CA; blue: cantharidin; brown: OA.

Figure 2

An overview of proven and hypothetical oxidative stress signaling pathways, where PP2A is involved. Red: Pathway 1; green: Pathway 2; Blue: Pathway 3. Clear lines/arrows show pathways that are already elucidated, while dashed lines/arrows show pathways for which some evidence exists, but further research is needed for clarification. The central player of these players is RBOH: the pathway of its expression and activation is controlled at multiple steps of Pathway 3 and it is also crucial for the production of apoplastic ROS, that will then re-enter Pathway 1 that is also controlled by PP2A. There is poor information on the regulation of Pathway 2 by PP2A. CPR5 is a phosphoregulated protein involved in SA signaling. CPK5 and ERK are Ca²⁺ activated protein kinases. OST1 (OPEN STOMATA 1) is a protein kinase involved in the activation of RBOH. OXI1 is a Ser/thr kinase and RLK/CRK is a large family of receptor-like kinases. PYR/RCAR is the ABA receptor and ABI1 and ABI2 are the PP2Cs inactivated by ABA.