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item Dardick, Christopher - Chris

Submitted to: Public Library of Science for Pathogens
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 12/14/2005
Publication Date: 1/20/2006
Citation: Dardick, C.D., Ronald, P. 2006. Plant and animal pathogen recognition receptors signal through non-rd kinases. Public Library of Science for Pathogens. 2(1):e2.

Interpretive Summary: Plants and animals have cellular defense systems that protect against invading microorganisms such as viruses, bacteria, and fungi. These defenses are dependent upon the ability of the host organism to “recognize” the presence of the invader and mount a successful counterattack. To accomplish this, cells contain a set of pathogen recognition receptors that function as pathogen surveillance proteins. These receptors rapidly activate defense signaling pathways following infection. Pathogen recognition receptors and components of their cellular signaling pathways share remarkable similarities in mammals, plants, and invertebrates such as insects and worms. Among these, a common group of signaling proteins, called kinases, associate with the receptors and are responsible for relaying signals and coordinating defense responses. Kinases are well known enzymes which, once activated, chemically modify and activate other downstream signaling proteins. This property enables kinases to send and amplify cellular signals that result in up or down regulation of specific genes. In the case of pathogen defense, such changes in gene regulation lead to the production of antimicrobial compounds and other defensive adaptations. Currently, scientists in both the medical and agricultural fields are targeting kinases to enhance natural defense systems and, in humans, find cures for genetic diseases caused by mutations in these genes. Such work requires detailed knowledge of how these kinases become activated, information that is currently lacking. In the present study, we have found that the kinases controlling defense responses in both plants and animals are regulated in a unique way. This discovery suggests that transmittance of pathogen recognition signals is to some extent functionally similar in plants and animals and distinct from other receptor-mediated signaling pathways such as growth and development. Understanding these differences will be critical to understanding how defenses are activated and more importantly, may impact therapeutic strategies designed to target these kinases. In addition, we provide a predictive tool to identify new kinases that also function in relaying pathogen recognition signals. In plants, (which in some cases contain thousands of kinases) this tool allows us to separate those that function in disease resistance from those that control other cellular processes. This study will be informative to a broad scientific readership including researchers studying pathogen defense systems in plants and animals as well as researchers studying kinases in general

Technical Abstract: Plant and animal innate immune systems share a number of striking similarities. Among these, the monophyletic group of kinases formed by Drosophila Pelle, Human IRAK, and members of the very large plant receptor kinase subfamily are known to play roles in pathogen recognition . In addition to their phylogenetic similarities, we have found that these kinases also fall into a small functional class of kinases termed non-RD. Non-RD kinases are named for the lack of a conserved arginine in kinase subdomain VI and, unlike the more common RD kinases, do not typically auto-phosphorylate a regulatory region called the activation loop. This suggests that the regulatory mechanisms of kinases mediating early steps of innate immunity signaling are conserved in plants and animals. We surveyed the human, fly, worm, Arabidopsis and rice kinomes (3,122 kinases) and found that despite the small number of non-RD kinases in these genomes (9-29%), nearly all kinases associated with pattern recognition receptors (PRRs) fall into the non-RD class. Few examples were found of non-RD kinases containing RD counterparts in another organism suggesting a high degree of evolutionary and functional conservation. Of the non-RD kinases surveyed, all with known functions in receptor-mediated pathways were associated with Rel/nuclear factor (NF)-kappa B activation and/or pathogen defense. Plant non-RD kinase subfamilies show evidence of recent lineage specific expansions also observed for the NOD-like NBS-LRR class of PRRs, supporting a role for plant non-RD kinases in innate immunity. The correlation between non-RD kinases and PRRs is significant (p = <0.0001).These data indicate that kinases controlling early steps in innate immune responses can largely be predicted by the lack of a single conserved residue.