PhosPhAt goes kinases—searchable protein kinase target information in the plant phosphorylation site database PhosPhAt

Reversible phosphorylation is a key mechanism for regulating protein function. Thus it is of high interest to know which kinase can phosphorylate which proteins. Comprehensive information about phosphorylation sites in Arabidopsis proteins is hosted within the PhosPhAt database (http://phosphat.mpimp-golm.mpg.de). However, our knowledge of the kinases that phosphorylate those sites is dispersed throughout the literature and very difficult to access, particularly for investigators seeking to interpret large scale and high-throughput experiments. Therefore, we aimed to compile information on kinase–substrate interactions and kinase-specific regulatory information and make this available via a new functionality embedded in PhosPhAt. Our approach involved systematic surveying of the literature for regulatory information on the members of the major kinase families in Arabidopsis thaliana, such as CDPKs, MPK(KK)s, AGC kinases and SnRKs, as well as individual kinases from other families. To date, we have researched more than 4450 kinase-related publications, which collectively contain information on about 289 kinases. Users can now query the PhosPhAt database not only for experimental and predicted phosphorylation sites of individual proteins, but also for known substrates for a given kinase or kinase family. Further developments include addition of new phosphorylation sites and visualization of clustered phosphorylation events, known as phosphorylation hotspots.

[1]  Joachim Selbig,et al.  PhosPhAt: a database of phosphorylation sites in Arabidopsis thaliana and a plant-specific phosphorylation site predictor , 2007, Nucleic Acids Res..

[2]  K. Harter,et al.  Plant two-component systems: principles, functions, complexity and cross talk , 2004, Planta.

[3]  Michael Gribskov,et al.  PlantsP: a functional genomics database for plant phosphorylation , 2001, Nucleic Acids Res..

[4]  Diego Mauricio Riaño-Pachón,et al.  Proteome-wide survey of phosphorylation patterns affected by nuclear DNA polymorphisms in Arabidopsis thaliana , 2010, BMC Genomics.

[5]  Sorina C. Popescu,et al.  MAPK target networks in Arabidopsis thaliana revealed using functional protein microarrays. , 2009, Genes & development.

[6]  M. Sussman,et al.  In planta changes in protein phosphorylation induced by the plant hormone abscisic acid , 2010, Proceedings of the National Academy of Sciences.

[7]  Kazuo Shinozaki,et al.  Mitogen-activated protein kinase cascades in plants: a new nomenclature. , 2002, Trends in plant science.

[8]  Heribert Hirt,et al.  Glycogen synthase kinase 3/SHAGGY-like kinases in plants: an emerging family with novel functions. , 2002, Trends in plant science.

[9]  G. Hong,et al.  Nucleic Acids Research , 2015, Nucleic Acids Research.

[10]  M. Tomita,et al.  Large-Scale Comparative Phosphoproteomics Identifies Conserved Phosphorylation Sites in Plants1[W][OA] , 2010, Plant Physiology.

[11]  Michel Zivy,et al.  Phospho-site mapping, genetic and in planta activation studies reveal key aspects of the different phosphorylation mechanisms involved in activation of SnRK2s. , 2010, The Plant journal : for cell and molecular biology.

[12]  Robert Schmidt,et al.  PhosPhAt: the Arabidopsis thaliana phosphorylation site database. An update , 2009, Nucleic Acids Res..

[13]  B. Roschitzki,et al.  Characterization of the phosphoproteome of mature Arabidopsis pollen. , 2012, The Plant journal : for cell and molecular biology.

[14]  Elliot M. Meyerowitz,et al.  Antagonistic Regulation of PIN Phosphorylation by PP2A and PINOID Directs Auxin Flux , 2007, Cell.

[15]  Joachim Selbig,et al.  Extension of the Visualization Tool MapMan to Allow Statistical Analysis of Arrays, Display of Coresponding Genes, and Comparison with Known Responses1 , 2005, Plant Physiology.

[16]  B. Turk,et al.  A versatile strategy to define the phosphorylation preferences of plant protein kinases and screen for putative substrates. , 2008, The Plant journal : for cell and molecular biology.

[17]  W. Schulze,et al.  Nitrate and ammonium lead to distinct global dynamic phosphorylation patterns when resupplied to nitrogen-starved Arabidopsis seedlings , 2012, The Plant journal : for cell and molecular biology.

[18]  Yan Xiong,et al.  Dual control of nuclear EIN3 by bifurcate MAPK cascades in C2H4 signalling , 2008, Nature.

[19]  Fang Huang,et al.  Phosphorylation of Conserved PIN Motifs Directs Arabidopsis PIN1 Polarity and Auxin Transport[W][OA] , 2010, Plant Cell.

[20]  Hans Lehrach,et al.  Arabidopsis PDK1: identification of sites important for activity and downstream phosphorylation of S6 kinase. , 2006, Biochimie.

[21]  Jürgen Kreutzberger,et al.  High Throughput Identification of Potential Arabidopsis Mitogen-activated Protein Kinases Substrates*S , 2005, Molecular & Cellular Proteomics.

[22]  S. Rhee,et al.  MAPMAN: a user-driven tool to display genomics data sets onto diagrams of metabolic pathways and other biological processes. , 2004, The Plant journal : for cell and molecular biology.

[23]  S. Shiu,et al.  Receptor-like kinases from Arabidopsis form a monophyletic gene family related to animal receptor kinases , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[24]  W. Gruissem,et al.  MASCP Gator: An Aggregation Portal for the Visualization of Arabidopsis Proteomics Data1[C][OA] , 2010, Plant Physiology.

[25]  Chunjiang Zhou,et al.  An Arabidopsis Mitogen-Activated Protein Kinase Cascade, MKK9-MPK6, Plays a Role in Leaf Senescence1[C][W][OA] , 2009, Plant Physiology.

[26]  Ying Sun,et al.  Brassinosteroid signal transduction from cell-surface receptor kinases to nuclear transcription factors , 2009, Nature Cell Biology.

[27]  Shoshi Kikuchi,et al.  CDPK-mediated abiotic stress signaling , 2012, Plant signaling & behavior.

[28]  Chris Mungall,et al.  AmiGO: online access to ontology and annotation data , 2008, Bioinform..

[29]  P. Coello,et al.  SnRK1 Isoforms AKIN10 and AKIN11 Are Differentially Regulated in Arabidopsis Plants under Phosphate Starvation1[C][OA] , 2009, Plant Physiology.

[30]  Rossana Henriques,et al.  Growth signalling pathways in Arabidopsis and the AGC protein kinases. , 2003, Trends in plant science.

[31]  S. Gygi,et al.  An iterative statistical approach to the identification of protein phosphorylation motifs from large-scale data sets , 2005, Nature Biotechnology.

[32]  K. Bretonnel Cohen,et al.  A critical review of PASBio's argument structures for biomedical verbs , 2006, BMC Bioinformatics.

[33]  Katja Baerenfaller,et al.  Taking the Next Step: Building an Arabidopsis Information Portal[OA] , 2012, Plant Cell.

[34]  G. Muday,et al.  PINOID Kinase Regulates Root Gravitropism through Modulation of PIN2-Dependent Basipetal Auxin Transport in Arabidopsis1[W][OA] , 2009, Plant Physiology.

[35]  Christopher J. Rawlings,et al.  An International Bioinformatics Infrastructure to Underpin the Arabidopsis Community , 2010, Plant Cell.

[36]  Michael Gribskov,et al.  The PlantsP and PlantsT Functional Genomics Databases , 2003, Nucleic Acids Res..

[37]  K. Mockaitis,et al.  Arabidopsis kinome: after the casting , 2004, Functional & Integrative Genomics.

[38]  Fang Huang,et al.  Plasma membrane-bound AGC3 kinases phosphorylate PIN auxin carriers at TPRXS(N/S) motifs to direct apical PIN recycling , 2010, Development.

[39]  Wolfram Weckwerth,et al.  Comparative analysis of phytohormone-responsive phosphoproteins in Arabidopsis thaliana using TiO2-phosphopeptide enrichment and mass accuracy precursor alignment. , 2010, The Plant journal : for cell and molecular biology.

[40]  Michel Zivy,et al.  The Arabidopsis ABA-Activated Kinase OST1 Phosphorylates the bZIP Transcription Factor ABF3 and Creates a 14-3-3 Binding Site Involved in Its Turnover , 2010, PloS one.

[41]  T. Hunter,et al.  The Protein Kinase Complement of the Human Genome , 2002, Science.

[42]  Rolf Apweiler,et al.  The Ontology Lookup Service, a lightweight cross-platform tool for controlled vocabulary queries , 2006, BMC Bioinformatics.

[43]  Klaus Palme,et al.  A PINOID-Dependent Binary Switch in Apical-Basal PIN Polar Targeting Directs Auxin Efflux , 2004, Science.

[44]  M. Gribskov,et al.  The Arabidopsis CDPK-SnRK Superfamily of Protein Kinases , 2003, Plant Physiology.

[45]  Gary D Bader,et al.  BMC Biology BioMed Central , 2007 .

[46]  Dirk Walther,et al.  Characterization and Prediction of Protein Phosphorylation Hotspots in Arabidopsis thaliana , 2012, Front. Plant Sci..

[47]  O. Jensen Modification-specific proteomics: characterization of post-translational modifications by mass spectrometry. , 2004, Current opinion in chemical biology.

[48]  T. Hunter A thousand and one protein kinases , 1987, Cell.