Integrative bioinformatics for kinase-concentric phosphorylation networks in Arabidopsis thaliana.

摘要

Phosphorylation, mediated by various types of protein kinases, is one of the most well studied mechanisms regulating signal transduction. The extensive studies produce a large amount of phosphorylation data, which are scattered and distributed in scientific articles and databases. However, lack of integrative PTM resources, especially in plants, makes it challenging for biological scientists to connect those fragmented data for systematic understanding and global analysis of PTMs. Here we developed an integrative bioinformatics approach combining text mining, data mining, protein ontology, visualization, and analysis methods, thereby facilitating PTM information integration and knowledge discovery in plants.;For Arabidopsis thaliana, we identified a list of the top 15 most literature-documented kinase names through RLIMS-P, a text-mining tool to extract phosphorylation information. The resulting kinase list included PDK1 and PID, which are two kinases involved in a wide range of cellular activities and auxin polar transport respectively. Text-mining results demonstrated that phosphorylation of PID by PDK1 is a primary step to activate PID kinase's regulatory role in auxin polar transport.;Moreover, given that 3 key Brassinosteroid (BR)-signaling components, BRI1, BAK1 and BIN2, were in the kinase list, we assume that BR-signaling pathway is enriched with phosphorylation events. BR is a plant steroid hormone essential not only for plant growth and development but also for the immune response. Previous studies have shown that BR directly binds to receptor-like kinase BRI1 and its co-receptor BAK1; and consequently activates the downstream signal transduction components including BSK1, CDG1, BSU1, BIN2, BZR1 and BZR2. Those 8 key components are connected through a series of phosphorylation events, leading to the expression of genome-wide BR-responsive genes. Thus, we combined text mining and data mining data to construct a BR-signaling protein phosphorylation network. The combined data showed that the BR-signaling pathway was interconnected with multiple pathways such as the defense-, stress- and auxin-regulatory networks. Specifically, we hypothesized that BIN2 phosphorylated BSK5 on S329 was in response to salt stress; and the interplay of BRI1 with SERK family proteins was involved in the regulation of anther development, cell death and innate immunity.;This thesis work demonstrates that our integrative approach facilitates the integration of discrete and fragmented data and construction of networks enriched with phosphorylation information, thereby prompting hypothesis generation and knowledge discovery.