Preventing inappropriate signals pre- and post- ligand perception by a toggle switch mechanism of ERECTA

• 成果类型: Article
• 署名作者: Chen, Liangliang; Maes, Michal; Cochran, Alicia M.; Avila, Julian R.; Derbyshire, Paul; Sklenar, Jan; Haas, Kelsey M.; Villen, Judit; Menke, Frank L. H.; Torii, Keiko U.
• 署名单位: Howard Hughes Medical Institute; University of Texas System; University of Texas Austin; University of Texas System; University of Texas Austin; Howard Hughes Medical Institute; University of Washington; University of Washington Seattle; University of Washington; University of Washington Seattle; UK Research & Innovation (UKRI); Biotechnology and Biological Sciences Research Council (BBSRC); John Innes Center; University of East Anglia; University of Washington; University of Washington Seattle; University of Washington; University of Washington Seattle; Harvard University; Massachusetts Institute of Technology (MIT); Broad Institute
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-13388
• DOI: 10.1073/pnas.2420196122
• 发表日期: 2025-01-28
• 关键词: receptor-like kinase; secretory peptide; protein-kinases; family genes; arabidopsis; bri1; phosphorylation; pattern; activation; bki1

摘要

Dynamic control of signaling events requires swift regulation of receptors at an active state. By focusing on the Arabidopsis ERECTA (ER) receptor kinase, which perceives peptide ligands to control multiple developmental processes, we report a mechanism preventing inappropriate receptor activity. The ER C- terminal tail (ER_CT) functions as an autoinhibitory domain: Its removal confers higher kinase activity and hyperactivity during inflorescence and stomatal development. ER_CT is required for the binding of a receptor kinase inhibitor, BKI1, and two U- box E3 ligases, PUB30 and PUB31, that trigger activated ER to degradation through ubiquitination. We further identify ER_CT as a phosphodomain transphosphorylated by the coreceptor BAK1. The phosphorylation impacts the tail structure, likely releasing ER from autoinhibition. The phosphonull version enhances BKI1 association, whereas the phosphomimetic version promotes PUB30/31 association. Thus, ER_CT acts as an off-on-off toggle switch, facilitating the release of BKI1 inhibition, enabling signal activation, and swiftly turning over the receptors afterward. Our results elucidate a mechanism that fine- tunes receptor signaling via a phosphoswitch module, maintaining the receptor at a low basal state while ensuring robust yet transient activation upon ligand perception.