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Chemoproteomics Reveals the Pan-HER Kinase Inhibitor Neratinib To Target an Arabidopsis Epoxide Hydrolase Related to Phytohormone Signaling by Sabrina Ninck; Vivek Halder; Jan H. Krahn; Daniela Beisser; Sarah Resch; Isobel Dodds; René Scholtysik; Jenny Bormann; Leonard Sewald; Mainak D. Gupta; Geronimo Heilmann; Deepak D. Bhandari; Kyoko Morimoto; Pierre Buscaill; Bettina Hause; Renier A. L. van der Hoorn; Farnusch Kaschani; Markus Kaiser is a Biochemistry, Genetics and Molecular Biology article available to read on EtoBox.

What is Chemoproteomics Reveals the Pan-HER Kinase Inhibitor Neratinib To Target an Arabidopsis Epoxide Hydrolase Related to Phytohormone Signaling about?

Plant phytohormone pathways are regulated by an intricate network of signaling components and modulators, many of which still remain unknown. Here, we report a forward chemical genetics approach for the identification of functional SA agonists in Arabidopsis thaliana that revealed Neratinib (Ner), a covalent pan-HER kinase inhibitor drug in humans, as a modulator of SA signaling. Instead of a protein kinase, chemoproteomics unveiled that Ner covalently modifies a surface-exposed cysteine residue of Arabidopsis epoxide hydrolase isoform 7 (AtEH7), thereby triggering its allosteric inhibition. Physiologically, the Ner application induces jasmonate metabolism in an AtEH7-dependent manner as an early response. In addition, it modulates PATHO-GENESIS RELATED 1 (PR1) expression as a hallmark of SA signaling activation as a later effect. AtEH7, however, is not the exclusive target for this physiological readout induced by Ner. Although the underlying molecular mechanisms of AtEH7-dependent modulation of jasmonate signaling and Ner-induced PR1dependent activation of SA signaling and thus defense response regulation remain unknown, our present work illustrates the powerful combination of fo

Who reads Chemoproteomics Reveals the Pan-HER Kinase Inhibitor Neratinib To Target an Arabidopsis Epoxide Hydrolase Related to Phytohormone Signaling?

Author

Sabrina Ninck; Vivek Halder; Jan H. Krahn; Daniela Beisser; Sarah Resch; Isobel Dodds; René Scholtysik; Jenny Bormann; Leonard Sewald; Mainak D. Gupta; Geronimo Heilmann; Deepak D. Bhandari; Kyoko Morimoto; Pierre Buscaill; Bettina Hause; Renier A. L. van der Hoorn; Farnusch Kaschani; Markus Kaiser

Publisher

American Chemical Society (ACS)

Published

2023

Language

EN

Field

Biochemistry, Genetics and Molecular Biology (Life Sciences)