Plant and Animal Pathogen Recognition Receptors Signal through Non-RD Kinases

Abstract

Plants and animals mediate early steps of the innate immune response through pathogen recognition receptors (PRRs). PRRs commonly associate with or contain members of a monophyletic group of kinases called the interleukin-1 receptor-associated kinase (IRAK) family that include Drosophila Pelle, human IRAKs, rice XA21 and Arabidopsis FLS2. In mammals, PRRs can also associate with members of the receptor-interacting protein (RIP) kinase family, distant relatives to the IRAK family. Some IRAK and RIP family kinases fall into a small functional class of kinases termed non-RD, many of which do not autophosphorylate the activation loop. We surveyed the yeast, fly, worm, human, Arabidopsis, and rice kinomes (3,723 kinases) and found that despite the small number of non-RD kinases in these genomes (9%–29%), 12 of 15 kinases known or predicted to function in PRR signaling fall into the non-RD class. These data indicate that kinases associated with PRRs can largely be predicted by the lack of a single conserved residue and reveal new potential plant PRR subfamilies.

Synopsis

Animal and plant innate immune systems use a set of similar receptors to recognize disease-causing microbes. These receptors function in pathogen surveillance and are located either at the cell surface or inside the cell. They provide a first line of defense against pathogen attack and rapidly activate defense signaling pathways following infection. Key to their ability to respond to pathogens, a closely related family of proteins called kinases either associate with these receptors or are present as part of the receptors themselves. These kinases face two challenges. The signals must be carefully modulated, as misregulation can result in disease and overall poor health. Second, these signaling systems must be resilient to attempts by pathogens to interfere with and block defense responses. The researchers have found that the kinases that are linked to pathogen receptors and initiate innate immune responses contain an alteration within a critical functional domain of the kinase that is not commonly found in similar kinases that control nondefense pathways. While the exact impact these changes have on kinase function is unclear, these findings provide insight into how these kinases may have evolved to compensate for the unique challenges they face. Moreover, they provide a predictive tool for identifying new candidate kinases that control innate immune responses.