PhosphoregDB: The tissue and sub-cellular distribution of mammalian protein kinases and phosphatases

BackgroundProtein kinases and protein phosphatases are the fundamental components of phosphorylation dependent protein regulatory systems. We have created a database for the protein kinase-like and phosphatase-like loci of mouse http://phosphoreg.imb.uq.edu.au that integrates protein sequence, interaction, classification and pathway information with the results of a systematic screen of their sub-cellular localization and tissue specific expression data mined from the GNF tissue atlas of mouse.ResultsThe database lets users query where a specific kinase or phosphatase is expressed at both the tissue and sub-cellular levels. Similarly the interface allows the user to query by tissue, pathway or sub-cellular localization, to reveal which components are co-expressed or co-localized. A review of their expression reveals 30% of these components are detected in all tissues tested while 70% show some level of tissue restriction. Hierarchical clustering of the expression data reveals that expression of these genes can be used to separate the samples into tissues of related lineage, including 3 larger clusters of nervous tissue, developing embryo and cells of the immune system. By overlaying the expression, sub-cellular localization and classification data we examine correlations between class, specificity and tissue restriction and show that tyrosine kinases are more generally expressed in fewer tissues than serine/threonine kinases.ConclusionTogether these data demonstrate that cell type specific systems exist to regulate protein phosphorylation and that for accurate modelling and for determination of enzyme substrate relationships the co-location of components needs to be considered.

[1]  Jun Kawai,et al.  LOCATE: a mouse protein subcellular localization database , 2005, Nucleic Acids Res..

[2]  T. Hunter,et al.  Evolution of protein kinase signaling from yeast to man. , 2002, Trends in biochemical sciences.

[3]  Susumu Goto,et al.  KEGG: Kyoto Encyclopedia of Genes and Genomes , 2000, Nucleic Acids Res..

[4]  Y. Hayashizaki,et al.  Protein-protein interaction panel using mouse full-length cDNAs. , 2001, Genome research.

[5]  S. Aaronson,et al.  Prokaryotic expression cloning of a novel human tyrosine kinase , 1994, Molecular and cellular biology.

[6]  Maria Deak,et al.  MSK1 activity is controlled by multiple phosphorylation sites. , 2005, The Biochemical journal.

[7]  Mark H. Ellisman,et al.  Hypophosphorylated SR splicing factors transiently localize around active nucleolar organizing regions in telophase daughter nuclei , 2004, The Journal of cell biology.

[8]  J. Sweatt,et al.  The neuronal MAP kinase cascade: a biochemical signal integration system subserving synaptic plasticity and memory , 2001, Journal of neurochemistry.

[9]  R. Flavell,et al.  Differentiation of CD4+ T cells to Th1 cells requires MAP kinase JNK2. , 1998, Immunity.

[10]  E. Birney,et al.  Analysis of the mouse transcriptome based on functional annotation of 60,770 full-length cDNAs , 2002, Nature.

[11]  A. Krogh,et al.  Predicting transmembrane protein topology with a hidden Markov model: application to complete genomes. , 2001, Journal of molecular biology.

[12]  Søren Brunak,et al.  Analysis and prediction of leucine-rich nuclear export signals. , 2004, Protein engineering, design & selection : PEDS.

[13]  Zhiyong Lu,et al.  Proteome Analyst: custom predictions with explanations in a web-based tool for high-throughput proteome annotations , 2004, Nucleic Acids Res..

[14]  Amos Bairoch,et al.  ScanProsite: a reference implementation of a PROSITE scanning tool. , 2002, Applied bioinformatics.

[15]  Hilmar Lapp,et al.  Large-scale profiling of Rab GTPase trafficking networks: the membrome. , 2005, Molecular biology of the cell.

[16]  Nikolaj Blom,et al.  Phospho.ELM: A database of experimentally verified phosphorylation sites in eukaryotic proteins , 2004, BMC Bioinformatics.

[17]  Rolf Apweiler,et al.  InterProScan: protein domains identifier , 2005, Nucleic Acids Res..

[18]  T. Hunter,et al.  The Croonian Lecture 1997. The phosphorylation of proteins on tyrosine: its role in cell growth and disease. , 1998, Philosophical transactions of the Royal Society of London. Series B, Biological sciences.

[19]  Thomas Huber,et al.  Phosphoregulators: protein kinases and protein phosphatases of mouse. , 2003, Genome research.

[20]  Michael Gribskov,et al.  PKR–the Protein Kinase Resource , 1997 .

[21]  Susumu Goto,et al.  The KEGG resource for deciphering the genome , 2004, Nucleic Acids Res..

[22]  T. Dale,et al.  Wnt signal transduction: kinase cogs in a nano-machine? , 2002, Trends in biochemical sciences.

[23]  M. Yaffe.  Phosphotyrosine-binding domains in signal transduction , 2002, Nature Reviews Molecular Cell Biology.

[24]  Ian M. Donaldson,et al.  BIND: the Biomolecular Interaction Network Database , 2001, Nucleic Acids Res..

[25]  Gary D Bader,et al.  BIND--The Biomolecular Interaction Network Database. , 2001, Nucleic acids research.

[26]  Xinglai Ji,et al.  BSubLoc: database of protein subcellular localization , 2004, Nucleic Acids Res..

[27]  Robert E. Lewis,et al.  Phosphorylation Regulates the Nucleocytoplasmic Distribution of Kinase Suppressor of Ras* , 2002, The Journal of Biological Chemistry.

[28]  Minoru Yoshida,et al.  CRM1 Is an Export Receptor for Leucine-Rich Nuclear Export Signals , 1997, Cell.

[29]  S. Batalov,et al.  A gene atlas of the mouse and human protein-encoding transcriptomes. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[30]  Sam A. Johnson,et al.  Kinomics: methods for deciphering the kinome , 2004, Nature Methods.

[31]  Alison A. McBride,et al.  Casein Kinase II Phosphorylation-induced Conformational Switch Triggers Degradation of the Papillomavirus E2 Protein* , 2004, Journal of Biological Chemistry.

[32]  T. Hunter,et al.  The mouse kinome: discovery and comparative genomics of all mouse protein kinases. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[33]  B. Rost,et al.  Finding nuclear localization signals , 2000, EMBO reports.

[34]  S. Brunak,et al.  Improved prediction of signal peptides: SignalP 3.0. , 2004, Journal of molecular biology.

[35]  P E Bourne,et al.  The protein kinase resource. , 1997, Trends in biochemical sciences.

[36]  Gabriele Ausiello,et al.  MINT: the Molecular INTeraction database , 2006, Nucleic Acids Res..

[37]  T. Hunter,et al.  The protein kinases of budding yeast: six score and more. , 1997, Trends in biochemical sciences.

[38]  Petri Auvinen,et al.  Mouse A6/Twinfilin Is an Actin Monomer-Binding Protein That Localizes to the Regions of Rapid Actin Dynamics , 2000, Molecular and Cellular Biology.

[39]  Zhirong Sun,et al.  Support vector machine approach for protein subcellular localization prediction , 2001, Bioinform..

[40]  N. Horike,et al.  Salt-inducible kinase-1 represses cAMP response element-binding protein activity both in the nucleus and in the cytoplasm. , 2004, European journal of biochemistry.

[41]  C. Marshall,et al.  Activation of MAP kinase kinase is necessary and sufficient for PC12 differentiation and for transformation of NIH 3T3 cells , 1994, Cell.