The EDR1–PP2A phospho-regulatory module fine-tunes MYC2-mediated plant disease resistance

Plants deploy sophisticated mechanisms to fine-tune plant immunity, as constitutive activation of disease resistance is detrimental. The Arabidopsis (Arabidopsis thaliana) Raf-like kinase ENHANCED DISEASE RESISTANCE 1 (EDR1) negatively regulates defense responses; however, how EDR1 functions and its phosphorylation substrates remain elusive. Here, we show that EDR1 interacts with and phosphorylates the transcription factor MYC2 at T353/T357. MYC2 positively regulates powdery mildew resistance, and the phosphorylation of MYC2 at T353/T357 by EDR1 inhibits its ability to bind to DNA and subsequently suppresses its function in powdery mildew resistance. MYC2 is dephosphorylated by protein phosphatase 2A (PP2A) Bɑ at T353/T357, which releases EDR1-mediated inhibition during infection to promote transcription and resistance. PP2A Bɑ is activated by MITOGEN-ACTIVATED KINASE 15 (MPK15), a positive regulator of powdery mildew resistance. Consistently, the pp2a bɑ mutant displays EDR1-dependent susceptibility to powdery mildew. Taken together, these results show that the activation of MYC2 is dynamically modulated by EDR1 and PP2A Bɑ in plant immunity. These findings not only expand our understanding of the roles of EDR1 and MYC2 but also reveal a mechanism by which plants fine-tune MYC2-mediated powdery mildew resistance via a dynamic phosphorylation regulatory module.