Battling Immune Kinases in Plants
Authors: Brad Day, Sheng Yang He
Journal: Cell Host & Microbe (2010)

As part of innate immune signaling, plants employ a suite of receptors, kinases, and resistance proteins to recognize pathogen-derived effector proteins. In this issue of Cell Host & Microbe, Zhang et al. provide evidence refining the link between multiple layers of defense signaling in response to bacterial pathogen infection. As part of innate immune signaling, plants employ a suite of receptors, kinases, and resistance proteins to recognize pathogen-derived effector proteins. In this issue of Cell Host & Microbe, Zhang et al. provide evidence refining the link between multiple layers of defense signaling in response to bacterial pathogen infection. Recent studies have highlighted the molecular-genetic arms race between the plant immune system and pathogen virulence effectors (reviewed in Chisholm et al., 2006Chisholm S.T. Coaker G. Day B. Staskawicz B.J. Cell. 2006; 124: 803-814Abstract Full Text Full Text PDF PubMed Scopus (1852) Google Scholar and Jones and Dangl, 2006Jones J.D. Dangl J.L. Nature. 2006; 444: 323-329Crossref PubMed Scopus (6981) Google Scholar). In particular, pathogen effectors often target the plant immune response network (Boller and He, 2009Boller T. He S.Y. Science. 2009; 324: 742-744Crossref PubMed Scopus (601) Google Scholar), and in return, plants refine and expand their immune system to defend against pathogens. In this issue of Cell Host & Microbe, Zhang et al., 2010Zhang J. Li W. Xiang T. Liu Z. Laluk K. Ding X. Zou Y. Gao M. Zhang X. Chen S. et al.Cell Host Microbe. 2010; 7 (this issue): 290-301Abstract Full Text Full Text PDF PubMed Scopus (471) Google Scholar, present evidence that several related Arabidopsis cytoplasmic receptor kinases, exemplified by botrytis-induced kinase 1 (BIK1) (Veronese et al., 2006Veronese P. Nakagami H. Bluhm B. Abuqamar S. Chen X. Salmeron J. Dietrich R.A. Hirt H. Mengiste T. Plant Cell. 2006; 18: 257-273Crossref PubMed Scopus (286) Google Scholar) and AvrPphB susceptible (PBS1) (Shao et al., 2003Shao F. Golstein C. Ade J. Stoutemyer M. Dixon J.E. Innes R.W. Science. 2003; 301: 1230-1233Crossref PubMed Scopus (404) Google Scholar), are cleaved by AvrPphB, a cysteine protease effector from the phytopathogenic bacterium Pseudomonas syringae. BIK1 turns out to be particularly important for plant immune responses, illustrating an excellent example of the utility of pathogen effectors as molecular probes in identifying new components of the plant immune system. This work also provides new insights as to how plants recognize the virulence action of AvrPphB and use it against bacterial infection. Innate immune signaling in plants is initiated as a consequence of the recognition of specific pathogen-associated molecular patterns (PAMP) by cognate plasma membrane-localized pathogen recognition receptors (PRRs). Collectively referred to as PAMP-triggered immunity (PTI) (Chisholm et al., 2006Chisholm S.T. Coaker G. Day B. Staskawicz B.J. Cell. 2006; 124: 803-814Abstract Full Text Full Text PDF PubMed Scopus (1852) Google Scholar, Jones and Dangl, 2006Jones J.D. Dangl J.L. Nature. 2006; 444: 323-329Crossref PubMed Scopus (6981) Google Scholar), this “layer” of host defense signaling is analogous to Toll-like receptor-mediated immune signaling in mammals and represents the first line of resistance activated in defense against pathogen infection. Following the recognition of pathogen effector molecules or their activities by plant disease resistance (R) proteins, effector-triggered immunity (Chisholm et al., 2006Chisholm S.T. Coaker G. Day B. Staskawicz B.J. Cell. 2006; 124: 803-814Abstract Full Text Full Text PDF PubMed Scopus (1852) Google Scholar, Jones and Dangl, 2006Jones J.D. Dangl J.L. Nature. 2006; 444: 323-329Crossref PubMed Scopus (6981) Google Scholar) results in both the amplification of PTI, as well as the specialization of defense signaling, and constitutes the second layer of defense. Recent work has provided evidence that PTI and ETI share common signaling networks and are connected via the action of pathogen effectors. In the current work, Zhang et al. present data that illustrate how the activity of AvrPphB links these connections. Previous work has shown that, in certain Arabidopsis accessions, after delivery into the host cell via the bacterial type III secretion system, AvrPphB is recognized by the cytoplasmic R protein RPS5, resulting in the activation of ETI (Shao et al., 2003Shao F. Golstein C. Ade J. Stoutemyer M. Dixon J.E. Innes R.W. Science. 2003; 301: 1230-1233Crossref PubMed Scopus (404) Google Scholar). As shown in Figure 1, the activation of RPS5-mediated resistance requires the catalytic activity of AvrPphB, which until now, was thought to cleave a single kinase, PBS1, in Arabidopsis (Shao et al., 2003Shao F. Golstein C. Ade J. Stoutemyer M. Dixon J.E. Innes R.W. Science. 2003; 301: 1230-1233Crossref PubMed Scopus (404) Google Scholar). Following cleavage of PBS1 by AvrPphB, it is thought that release of PBS1 from RPS5 induces a conformational change in RPS5 (and/or associated resistance complex), resulting in the activation of events required for the initiation of a sustained ETI response. In total, the AvrPphB-initiated ETI is sufficient to abrogate pathogen growth and halt further infection. Zhang and colleagues now show that, in addition to cleavage of PBS1, AvrPphB targets ∼10 PBS1-like (PBL) kinases, including BIK1, PBL1, PBL2, and PBS1. This is a significant finding, as it not only implicates BIK1 and additional kinases as potential links between multiple pathogen recognition events in plants, but it also lends itself to the question: What are the true virulence targets of AvrPphB? Based on extensive genetic and biochemical analyses, Zhang and colleagues propose that BIK1 and possibly other PBL kinases function to integrate immune responses activated via multiple PAMP receptors, such as FLS2 (Arabidopsis flagellin receptor) (Gómez-Gómez and Boller, 2000Gómez-Gómez L. Boller T. Mol. Cell. 2000; 5: 1003-1011Abstract Full Text Full Text PDF PubMed Google Scholar), EFR (receptor for bacterial EF-Tu) (Zipfel et al., 2006Zipfel C. Kunze G. Chinchilla D. Caniard A. Jones J.D. Boller T. Felix G. Cell. 2006; 125: 749-760Abstract Full Text Full Text PDF PubMed Scopus (1139) Google Scholar), and CERK1 (chitin receptor) (Miya et al., 2007Miya A. Albert P. Shinya T. Desaki Y. Ichimura K. Shirasu K. Narusaka Y. Kawakami N. Kaku H. Shibuya N. Proc. Natl. Acad. Sci. USA. 2007; 104: 19613-19618Crossref PubMed Scopus (824) Google Scholar). The current work demonstrates that BIK1 interacts with FLS2 in unstimulated plant cells, is rapidly phosphorylated, and is subsequently released from FLS2 upon FLS2 activation by its ligand, flg22. The ligand-dependent release of BIK1 from FLS2 is in striking contrast to the previously described ligand-dependent complex formation between FLS2 and BAK1, a coreceptor of FLS2. Zhang et al. proposed a model in which FLS2, BAK1, and BIK1 form a signaling relay through phosphorylation and physical interaction/dissociation. Although the full mechanism of this interaction needs to be worked out, this model seems to be generally in line with that proposed recently by Lu et al., 2010Lu D. Wu S. Gao X. Zhang Y. Shan L. He P. Proc. Natl. Acad. Sci. USA. 2010; 107: 496-501Crossref PubMed Scopus (459) Google Scholar, who independently discovered a critical role for BIK1 in PTI signaling. The identification of BIK1, PBS1, and other PBL kinases as substrates of AvrPphB, as well as the identification of the BIK1-FLS2 association in the present study provides strong evidence that AvrPphB links PTI and ETI and that kinase regulation may be a shared feature of both layers of defense signaling in plants. This is an interesting finding, as it opens the door to future work aimed at identifying the function of other PBL kinase targets, both in the presence and absence of pathogen. One interesting hypothesis is that the host has evolved multiple PBL targets as part of a more expansive surveillance mechanism. However, it is also possible that the work described herein has, in fact, identified the true virulence function of AvrPphB and, as such, would indicate that AvrPphB targets multiple host kinases involved in PTI defense signaling. In support of this hypothesis, genetic data presented by Zhang et al. suggest that the functions of BIK1, PBL1, PBL2, and PBS1 in PTI are additive; PBS1 has a minor role in PTI, whereas the bik1/pbl1 mutant is significantly impaired in PTI. Though the full details of the AvrPphB-RPS5-PBL network are unknown, the current work brings us one step closer to understanding the regulatory circuitry that specifies recognition and activation of immune signaling in plants. This work provides strong evidence bridging the gap between PTI and ETI through the virulence function of pathogen effector proteins. Future work aimed at identifying the function of PBLs, as well as BIK1, in the absence of pathogen infection will likely provide insight into the evolution of host-pathogen interactions, both in terms of virulence and pathogenicity, as well as conservation of shared and/or overlapping immune signaling pathways.