Perception of extracellular signals by cell surface receptors is of central importance to eukaryotic development and immunity. Many of these receptors possess intrinsic protein kinase activity in their cytoplasmic domains (RKs) and regulate transcription of target genes through phosphorylation and dephosphorylation events. Abnormal regulation can lead to a variety of diseases and it is therefore important to understand how RK specificity and function are controlled. In contrast to most protein kinases that are regulated by phosphorylation of the activation segment, a centrally located loop that sits close to the catalytic center, an emerging theme for some RKs is that the juxtamembrane (JM) domain plays a key regulatory role in their activation. In this case, residues in the JM domain perform both positive and negative regulatory functions. In their unphosphorylated state they repress catalytic activity and upon phosphorylation they serve as high affinity binding sites for downstream signaling proteins. Regulation of RK signaling through the JM domain is so far unique to only a few receptor families controlling important cellular processes and consequently there is great interest in exploring the molecular basis for this control. The rice XA21 gene, encoding a RK with leucine rich repeats (LRRs) in the extracellular domain, is a key recognition and signaling determinant in the innate immune response, a pathogen defense pathway widely conserved between plants and animals. XA21 is not autophosphorylated in the activation segment and at least four XA21 binding proteins (Xbs) require phosphorylated residues in the JM region for interaction. These include Xb10, encoding a putative transcriptional regulator and Xb15 encoding a PP2c phosphatase-like protein. Based on these results we hypothesize that the XA21 JM domain plays a key role in XA21 kinase-mediated signal transduction and that JM-binding protein's act as positive or negative regulators to control transcription of defense related genes. To further test this hypothesis we propose to: 1. Determine the role of Xb10 and Xb15 in Xa2'l -mediated and flagellin-activated defense responses. 2. Further characterize the XA21 JM domain, identify Xb kinase interaction domains and assess the role of XA21-dependent phosphorylation 3. Characterize the cellular interactions of XA2jl and Xbs and identify new components in the in vivo complexes.
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