Immunity of an entire plant species to infection by a particular pathogen species (non-host resistance) is determined by intertwined layers of defense including both constitutive barriers and inducible reactions. Activation of inducible defense responses is likely based upon recognition of pathogen-associated molecular patterns (PAMP), which bind to plant receptors. We have identified a calcium-dependent cell wall transglutaminase (TGase, EC 18.104.22.168) from various species of the phytopathogenic oomycete genus, Phytophthora, that triggers defense responses in parsley and potato. Transcripts encoding TGase were expressed and enzyme activity was detectable in 10 Phytophthora species analyzed. A surface-exposed fragment (Pep-13) of this protein, which is sufficient for receptor-mediated activation of pathogen defense, is highly conserved in all Phytophthora TGases. Mutational analysis within the Pep-13 sequence revealed amino acid residues indispensible for both transglutaminase activity and activation of plant defense. Thus, PAMPs (such as Pep-13) recognized by plants show similiarities to those triggering innate immune responses in mammals or Drosophila. Ligand-induced receptor activation results in elevated levels of cytoplasmic [Ca2+], which is likely due to influx through plasma membrane [Ca2+] channels. [Ca2+]-dependent production of superoxide anions and activation of MAP kinase cascades are implicated in the activation of transcription factors which mediate the expression of plant defense responses. Phytopathogenic bacteria of the genus Pseudomonas produce and secrete the effector protein, HrpZ, during (attempted) infection of plants. HrpZ was shown to insert into lipid bilayer membranes and to evoke cation-conducting channels. This ion channel-forming activity, however, does not form the molecular basis for the activation of defense responses in plants treated with HrpZ, but likely reflects the function of the protein in bacterial pathogenesis. Receptor-mediated activation of plant defense was rather shown to occur in parsley and tobacco.