The identification of MEKK1-MKK1/2-MPK4 in pathogen signaling has been a tremendous finding. Mekk1, mkk1/mkk2 double and mpk4 mutations are dwarfed and acquire too much of reactive oxygen species. The mutations are considered to be from the enhancement of SA levels, which is partially reversed by bacterial SA hydrolase. Mekk1, mkk1/mkk2 double and mpk4 mutations have cell death occur spontaneously, pathogenesis-related genes and increased resistance to pathogens. MEKK1 appears to have deregulation pathways that are unknown and do not involve MKK1/MKK2 nor MPK4. MEKK1 interact with WRKY53, which is responsible for mekk1 genes set, and alter the activity of WRKY53 that is a short portion of MAPK signaling. Substrates of MPK4 are three proteins: WRKY33, WRKY25, and MKS1. Ternary MKS1-MPK4-WRKY33 complexes have been recognized by nuclear extracts. Recruitment of WRKY33 depends on the phosphorylation of MPK4. Once activated, MPK3 phosphorylates MKS1, which releases WRKY33 from the ternary complex. The free WRKY33 is believed to induce transcription on target genes., allowing for a negative regulation by MPK4. Pathogens have developed mechanisms that inactivate PAMP-induced signaling pathways through the MAPK networks. Andrea Pitzschke and her colleges claim “AvrPto and AvrPtoB interact with the FLS2 receptor and its co-receptor BAK1. AvrPtoB catalyzes the polyubiquitination and subsequent proteasome-dependent degradation of FLS2” (Pitzschke 3). AvrPto interacts with BAK1 and interrupts the binding of FLS2. Pseudomonas syringae have HopAI1, which is a phosphothreonin lyase, and dephosphorylates the threonine residue at the upstream MAPKKs. HopAI1 interacts with MPK3 and MPK6 allowing for flg22 activation to occur. In certain soil-borne pathogens that carry flagellin variants cannot be detected by FLS2, but there is still a triggered innate immune response. The immune response has been shown to be from the EF-Tu protein. Flg22, elf18, FLS2 and EFR have receptors that are in the same subfamily of LRR-RLKs, LRRXII. This means that elf18 and flg22 induce extracellular alkalization, rapid activation of MAPKs, and gene responses that are similar to each other. Although there appears to be an important relationship between MAPKs with EF-Tu-triggered defense, the evidence remains to be unclear. The reason for this unclear relationship is because of Agrobacterium tumefaciens, which infects into segments of plant DNA.  EFR1 mutants do not recognize EF-Tu, but there is no research on MAPK activities and efr1. Initiation of defense signaling can be a positive effect to the plant pathogens because activating MPK3 in response to flg22 causes phosphorylation and translocation of virE2 interacting protein 1 (VIP1). VIP1 serves as a shuttle for the pathogenic T-DNA, but the induction of defense genes can occur as well. This allows for the spreading and cessation of the pathogen in the plant, but the pathogen can overcome the problem by attacking VIP1 for proteasome degradation by VirF, which is a virulence factor that encodes an F-box protein.