Validation of serine/threonine protein phosphatase as the herbicide target site of endothall

Endothall, an older commercial herbicide, and cantharidin, a natural product from the blister beetle (Epicauta spp.), are close chemical analogues. A comparison of the effect of endothall and cantharidin on plants revealed a similarity in their level of phytotoxicity on both Arabidopsis thaliana and Lemna paucicostata. Cantharidin is a potent inhibitor of animal serine/threonine protein phosphatases. Protein phosphatases and kinases maintain a sensitive balance between phosphorylated and dephosphorylated forms of proteins playing important roles in signal transduction pathways. In this study, we found endothall and cantharidin to both completely inhibit plant serine/threonine protein phosphatases, and their relative inhibitory activities were similar to their relative phytotoxicities. Both compounds acted as slow, irreversible inactivators of the serine/threonine protein phosphatase activities. Transcription of several genes determined to be affected by the inhibition of these protein phosphatases by cantharidin in A. thaliana by transcriptome analyses were affected similarly by endothall, but in a more pronounced way. Therefore, the molecular target site of endothall in plants is similar to that of cantharidin in animals, namely, serine/threonine protein phosphatases responsible for regulating an array of biochemical processes. This mode of action is unlike any other commercial herbicide.

Graphical abstractFigure optionsDownload full-size imageDownload as PowerPoint slideHighlights► Endothall and cantharidin inhibit serine/threonine protein phosphatases from plants. ► Serine/threonine protein phosphatase inhibition correlated with phytotoxicity. ► Both inhibitors acted as slow, irreversible inactivators of the enzymes. ► The effects of both inhibitors on transcription of several genes were similar. ► Serine/threonine phosphatases appear to be the molecular target sites of endothall.