Mitogen-activated protein kinase (MAPK) pathways have a pivotal role in innate immunity signaling in plants. In Arabidopsis, the MAPK pathway that consists of MEKK1, MKK1/MKK2 and MPK4 is involved in pattern-triggered immunity signaling upstream of defense gene expression. This pathway is partly guarded by SUMM2, a nucleotide-binding domain leucine-rich repeat (NLR) protein, which is activated by disruption of the MAPK pathway. To identify other components required for the guard mechanism, here we developed a new mutant screening system utilizing a dwarf autoimmune line that overexpressed the N-terminal regulatory domain of MEKK1. Mutants with suppression of the dwarf, autoimmune phenotypes were identified, and one locus responsible for the phenotype was designated as suppressor of MEKK1N overexpression-induced dwarf 1 (SMN1). MutMap analysis revealed that SMN1 encodes the Toll/Interleukin-1 receptor (TIR)-class NLR protein RPS6, a previously identified resistant protein against bacterial pathogen Pseudomonas syringae pv. tomato expressing the HopA1 effector. Importantly, mutations in SMN1/RPS6 also partially suppressed the dwarf, autoimmune phenotypes of mekk1 and mpk4 plants. Our results suggest that the two structurally distinct NLR proteins, SMN1/RPS6 and SUMM2, monitor integrity of the MEKK1-MKK1/MKK2-MPK4 pathway.