Plants and animals rely on immune sensory complexes to detect infection by recognizing evolutionarily conserved pathogen components. Plant immune senor FLS2, a structural and functional ortholog of mammalian Toll-like receptors (TLR), recognizes bacterial flagellin and initiates immune signaling by association with a receptor-like kinase BAK1. It remains unknown how FLS2/BAK1 receptor complex activates intracellular signaling cascades. We have identified two important phosphorylation substrates of BAK1 kinase. BIK1, an FLS2/BAK1-associated cytosolic kinase, is rapidly phosphorylated and released from FLS2/BAK1 receptor complex upon flagellin perception to propagate immune signaling. FCU, an E3 ubiquitin ligase, associates with FLS2 upon flagellin stimulation and ubiquitinates FLS2 receptor. BIK1 transphosphorylates BAK1/FLS2, which in turn enhances BAK1 phosphorylation on FCU. The objective of this application is to examine the role of BIK1 and FCU as convergent components in transducing innate immune signaling from receptor complexes to downstream intracellular events, and the biological significance of phosphorylation and ubiquitination in activating and regulating immune sensory complexes.
Three specific aims are 1) Elucidate the role of receptor-associated kinase in innate immune signaling. 2) Determine the function of E3 ubiquitin ligase in innate immune signaling. 3) Characterize the ubiquitination of PAMP receptor complexes. Recent advance on the molecular architecture of nonself recognition has revealed remarkable conservation in the mechanisms of microbial perception and innate immune signaling in multicellular eukaryotes. Phosphorylation and ubiquitination are two key mechanisms in regulating many cellular and organismal processes, including innate immunity. The power of Arabidopsis genetics and genomics provides an excellent model to understand the functions of these two universal regulatory mechanisms at the whole organism level. Thus, the proposed research will provide new insight on signal transduction in general and contribute to the understanding of innate immune signaling and immune sensory complex function.

Public Health Relevance

Phosphorylation and ubiquitination are two key mechanisms in regulating many cellular and organismal processes in different organisms. Deciphering the molecular and biochemical mechanisms of immune sensory complex regulation and activation by phosphorylation and ubiquitination will contribute to our general understanding of cellular signaling and host innate immunity. Given the considerable similarities of innate immunity among multicellular eukaryotes, we anticipate that our research will have broad impact on the study of innate immunity and signal transduction in general.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM097247-02
Application #
8291246
Study Section
Cellular Signaling and Regulatory Systems Study Section (CSRS)
Program Officer
Dunsmore, Sarah
Project Start
2011-07-01
Project End
2016-04-30
Budget Start
2012-05-01
Budget End
2013-04-30
Support Year
2
Fiscal Year
2012
Total Cost
$243,249
Indirect Cost
$73,249
Name
Texas A&M University
Department
Other Basic Sciences
Type
Schools of Earth Sciences/Natur
DUNS #
078592789
City
College Station
State
TX
Country
United States
Zip Code
77845
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