biostudies-literaturePaulus JKEuropean Research CouncilRCUK | Biotechnology and Biological Sciences Research CouncilClarendon FundEC | FP7 | FP7 People: Marie-Curie ActionsBiotechnology and Biological Sciences Research Council17409-17417https://www.ebi.ac.uk/biostudies/studies/S-EPMC7382257biostudies-literatureUnknown117(29)Proteolytic cascades regulate immunity and development in animals, but these cascades in plants have not yet been reported. Here we report that the extracellular immune protease Rcr3 of tomato is activated by P69B and other subtilases (SBTs), revealing a proteolytic cascade regulating extracellular immunity in solanaceous plants. Rcr3 is a secreted papain-like Cys protease (PLCP) of tomato that acts both in basal resistance against late blight disease (Phytophthora infestans) and in gene-for-gene resistance against the fungal pathogen Cladosporium fulvum (syn. Passalora fulva) Despite the prevalent model that Rcr3-like proteases can activate themselves at low pH, we found that catalytically inactive proRcr3 mutant precursors are still processed into mature mRcr3 isoforms. ProRcr3 is procesProceedings of the National Academy of Sciences of the United States of AmericaExtracellular proteolytic cascade in tomato activates immune protease Rcr3.PMC7382257n/aBBS/E/J/000PR9797BB/S003193/1ITN ProtectaInterdisciplinary DTC616449Kourelis JGodson AKamoun SPaulus JKOssorio Carballo LKrahn Dvan der Hoorn RALDong SHong TNWang SSmoker MHorger ACRamasubramanian SHomma FWin JfalseExtracellular proteolytic cascade in tomato activates immune protease Rcr3.Proteolytic cascades regulate immunity and development in animals, but these cascades in plants have not yet been reported. Here we report that the extracellular immune protease Rcr3 of tomato is activated by P69B and other subtilases (SBTs), revealing a proteolytic cascade regulating extracellular immunity in solanaceous plants. Rcr3 is a secreted papain-like Cys protease (PLCP) of tomato that acts both in basal resistance against late blight disease (Phytophthora infestans) and in gene-for-gene resistance against the fungal pathogen Cladosporium fulvum (syn. Passalora fulva) Despite the prevalent model that Rcr3-like proteases can activate themselves at low pH, we found that catalytically inactive proRcr3 mutant precursors are still processed into mature mRcr3 isoforms. ProRcr3 is proces2020-01-01T00:00:00Z2020 Jul2025-04-04T08:18:29.019Z2025-04-04T08:18:29.019ZS-EPMC73822573261656710.1073/pnas.1921101117