Thu, 21 Aug 2008 06:50:06 BST CiteULike: renatomilani's kinome http://www.citeulike.org/user/renatomilani/tag/kinome CiteULike.org en-gb Copyright © 2004-2008 citeulike.org http://www.citeulike.org/user/renatomilani/article/2707968 <i>Trends in Biochemical Sciences, Vol. 27, No. 10. (1 October 2002), pp. 514-520.</i><br /><br />Protein phosphorylation controls many cellular processes, especially those involved in intercellular communication and coordination of complex functions. To explore the evolution of protein phosphorylation, we compared the protein kinase complements ([`]kinomes') of budding yeast, worm and fly, with known human kinases. We classify kinases into putative orthologous groups with conserved functions and discuss kinase families and pathways that are unique, expanded or lost in each lineage. Fly and human share several kinase families involved in immunity, neurobiology, cell cycle and morphogenesis that are absent from worm, suggesting that these functions might have evolved after the divergence of nematodes from the main metazoan lineage. Evolution of protein kinase signaling from yeast to man Gerard Manning Gregory Plowman Tony Hunter Sucha Sudarsanam doi:10.1016/S0968-0004(02)02179-5 Trends in Biochemical Sciences, Vol. 27, No. 10. (1 October 2002), pp. 514-520. 2008-04-23T15:32:06-00:00 2002 Trends in Biochemical Sciences 27 10 514 520 evolution kinase kinome http://www.citeulike.org/user/renatomilani/article/4709 <i>Nature Methods, Vol. 2, No. 1. (21 December 2004), 17.</i> Kinomics: methods for deciphering the kinome Sam Johnson Tony Hunter doi:10.1038/nmeth731 Nature Methods, Vol. 2, No. 1. (21 December 2004), 17. 2004-12-23T14:17:46-00:00 2004 Nature Methods 2 1 17 kinome http://www.citeulike.org/user/renatomilani/article/2906078 <i>Genome biology, Vol. 3, No. 9. (22 August 2002)</i><br /><br />BACKGROUND: Eukaryotic protein kinases (EPKs) constitute one of the largest recognized protein families represented in the human genome. EPKs, which are similar to each other in sequence, structure and biochemical properties, are important players in virtually every signaling pathway involved in normal development and disease. Near completion of projects to sequence the human genome and transcriptome provide an opportunity to identify and perform sequence analysis on a nearly complete set of human EPKs. RESULTS: Publicly available genetic sequence data were searched for human sequences that potentially represent EPK family members. After removal of duplicates, splice variants and pseudogenes, this search yielded 510 sequences with recognizable similarity to the EPK family. Protein sequences of putative EPK catalytic domains identified in the search were aligned, and a phonogram was constructed based on the alignment. Representative sequence records in GenBank were identified, and derived information about gene mapping and nomenclature was summarized. CONCLUSIONS: This work represents a nearly comprehensive census and early bioinformatics overview of the EPKs encoded in the human genome. Evaluation of the sequence relationships between these proteins contributes contextual information that enhances understanding of individual family members. This curation of human EPK sequences provides tools and a framework for the further characterization of this important class of enzymes. Human members of the eukaryotic protein kinase family. M Kostich J English V Madison F Gheyas L Wang P Qiu J Greene TM Laz Genome biology, Vol. 3, No. 9. (22 August 2002) 2008-06-18T19:39:26-00:00 2002 Genome biology 1465-6914 3 9 kinase kinome http://www.citeulike.org/user/renatomilani/article/2042380 <i>Protein Pept Lett, Vol. 14, No. 6. (2007), pp. 509-517.</i><br /><br />Phosphorylation by protein kinases is a very common and crucial process in many signal transduction pathways in eukaryotes. This review describes comparative protein kinase analysis of two apicomplexa Plasmodium falciparum (3D7 strain) and Plasmodium yoelii yoelii (17XNL strain) which are causative agents of malaria in human and African rat respectively. Sensitive bioinformatics techniques enable identification of 82 and 60 putative protein kinases in P. falciparum and P. yoelii yoelii respectively and these sequences could be classified into known subfamilies of protein kinases. The most populated kinase subfamilies in both the plasmodium species correspond to CAMK and CMGC groups. Analysis of domain architectures enables detection of uncommon domain organization in kinases of both the organisms such as kinase domain tethered to EF hands as well as PH domain. Components of MAPK signaling pathway is not well conserved in plasmodium organisms. Such observations suggest that plasmodium protein kinases are highly divergent from other eukaryotes. A transmembrane kinase with 6 membrane spanning segments in P. falciparum seems to have no orthologue in P. yoelii yoelii. 19 P. falciparum kinases have been found to cluster separately from P. yoelii yoelii kinases and hence these kinases are unique to P. falciparum genome. Only 28 orthologous pairs of kinases seem to be present between these two plasmodium organisms. Comparative kinome analysis of two plasmodium species has thus provided clues to the function of many protein kinases based upon their classification and domain organization and also implicate marked differences even between two plasmodium organisms. Comparative kinomics of Plasmodium organisms: unity in diversity. K Anamika N Srinivasan Protein Pept Lett, Vol. 14, No. 6. (2007), pp. 509-517. 2007-12-02T07:25:13-00:00 2007 Protein Pept Lett 0929-8665 14 6 509 517 kinome malaria http://www.citeulike.org/user/renatomilani/article/1187602 <i>BMC Genomics, Vol. 6 (2005)</i><br /><br />BACKGROUND: The trypanosomatids Leishmania major, Trypanosoma brucei and Trypanosoma cruzi cause some of the most debilitating diseases of humankind: cutaneous leishmaniasis, African sleeping sickness, and Chagas disease. These protozoa possess complex life cycles that involve development in mammalian and insect hosts, and a tightly coordinated cell cycle ensures propagation of the highly polarized cells. However, the ways in which the parasites respond to their environment and coordinate intracellular processes are poorly understood. As a part of an effort to understand parasite signaling functions, we report the results of a genome-wide analysis of protein kinases (PKs) of these three trypanosomatids. RESULTS: Bioinformatic searches of the trypanosomatid genomes for eukaryotic PKs (ePKs) and atypical PKs (aPKs) revealed a total of 176 PKs in T. brucei, 190 in T. cruzi and 199 in L. major, most of which are orthologous across the three species. This is approximately 30% of the number in the human host and double that of the malaria parasite, Plasmodium falciparum. The representation of various groups of ePKs differs significantly as compared to humans: trypanosomatids lack receptor-linked tyrosine and tyrosine kinase-like kinases, although they do possess dual-specificity kinases. A relative expansion of the CMGC, STE and NEK groups has occurred. A large number of unique ePKs show no strong affinity to any known group. The trypanosomatids possess few ePKs with predicted transmembrane domains, suggesting that receptor ePKs are rare. Accessory Pfam domains, which are frequently present in human ePKs, are uncommon in trypanosomatid ePKs. CONCLUSION: Trypanosomatids possess a large set of PKs, comprising approximately 2% of each genome, suggesting a key role for phosphorylation in parasite biology. Whilst it was possible to place most of the trypanosomatid ePKs into the seven established groups using bioinformatic analyses, it has not been possible to ascribe function based solely on sequence similarity. Hence the connection of stimuli to protein phosphorylation networks remains enigmatic. The presence of numerous PKs with significant sequence similarity to known drug targets, as well as a large number of unusual kinases that might represent novel targets, strongly argue for functional analysis of these molecules. Comparative analysis of the kinomes of three pathogenic trypanosomatids: Leishmania major, Trypanosoma brucei and Trypanosoma cruzi. M Parsons EA Worthey PN Ward JC Mottram doi:10.1186/1471-2164-6-127 BMC Genomics, Vol. 6 (2005) 2007-03-26T07:16:58-00:00 2005 BMC Genomics 1471-2164 6 kinome http://www.citeulike.org/user/renatomilani/article/984616 <i>PLoS Genetics, Vol. 2, No. 3. (1 March 2006), e38.</i><br /><br />Dictyostelium discoideum is a widely studied model organism with both unicellular and multicellular forms in its developmental cycle. The Dictyostelium genome encodes 285 predicted protein kinases, similar to the count of the much more advanced Drosophila. It contains members of most kinase classes shared by fungi and metazoans, as well as many previously thought to be metazoan specific, indicating that they have been secondarily lost from the fungal lineage. This includes the entire tyrosine kinase–like (TKL) group, which is expanded in Dictyostelium and includes several novel receptor kinases. Dictyostelium lacks tyrosine kinase group kinases, and most tyrosine phosphorylation appears to be mediated by TKL kinases. About half of Dictyostelium kinases occur in subfamilies not present in yeast or metazoa, suggesting that protein kinases have played key roles in the adaptation of Dictyostelium to its habitat. This study offers insights into kinase evolution and provides a focus for signaling analysis in this system. The Dictyostelium Kinome—Analysis of the Protein Kinases from a Simple Model Organism Jonathan Goldberg Gerard Manning Allen Liu Petra Fey Karen Pilcher Yanji Xu Janet Smith doi:10.1371/journal.pgen.0020038 PLoS Genetics, Vol. 2, No. 3. (1 March 2006), e38. 2006-12-08T18:04:14-00:00 2006 PLoS Genetics 2 3 e38 kinome http://www.citeulike.org/user/renatomilani/article/90450 <i>Proc Natl Acad Sci U S A, Vol. 101, No. 32. (10 August 2004), pp. 11707-11712.</i><br /><br />We have determined the full protein kinase (PK) complement (kinome) of mouse. This set of 540 genes includes many novel kinases and corrections or extensions to >150 published sequences. The mouse has orthologs for 510 of the 518 human PKs. Nonorthologous kinases arise only by retrotransposition and gene decay. Orthologous kinase pairs vary in sequence conservation along their length, creating a map of functionally important regions for every kinase pair. Many species-specific sequence inserts exist and are frequently alternatively spliced, allowing for the creation of evolutionary lineage-specific functions. Ninety-seven kinase pseudogenes were found, all distinct from the 107 human kinase pseudogenes. Chromosomal mapping links 163 kinases to mutant phenotypes and unlocks the use of mouse genetics to determine functions of orthologous human kinases. The mouse kinome: discovery and comparative genomics of all mouse protein kinases. S Caenepeel G Charydczak S Sudarsanam T Hunter G Manning doi:10.1073/pnas.0306880101 Proc Natl Acad Sci U S A, Vol. 101, No. 32. (10 August 2004), pp. 11707-11712. 2005-02-08T22:19:26-00:00 2004 Proc Natl Acad Sci U S A 0027-8424 101 32 11707 11712 kinome http://www.citeulike.org/user/renatomilani/article/2906069 <i>Developmental biology, Vol. 300, No. 1. (1 December 2006), pp. 180-193.</i><br /><br />This paper reports a preliminary in silico analysis of the sea urchin kinome. The predicted protein kinases in the sea urchin genome were identified, annotated and classified, according to both function and kinase domain taxonomy. The results show that the sea urchin kinome, consisting of 353 protein kinases, is closer to the Drosophila kinome (239) than the human kinome (518) with respect to total kinase number. However, the diversity of sea urchin kinases is surprisingly similar to humans, since the urchin kinome is missing only 4 of 186 human subfamilies, while Drosophila lacks 24. Thus, the sea urchin kinome combines the simplicity of a non-duplicated genome with the diversity of function and signaling previously considered to be vertebrate-specific. More than half of the sea urchin kinases are involved with signal transduction, and approximately 88% of the signaling kinases are expressed in the developing embryo. These results support the strength of this nonchordate deuterostome as a pivotal developmental and evolutionary model organism. The sea urchin kinome: a first look. CA Bradham KR Foltz WS Beane MI Arnone F Rizzo JA Coffman A Mushegian M Goel J Morales AM Geneviere F Lapraz AJ Robertson H Kelkar M Loza-Coll IK Townley M Raisch MM Roux T Lepage C Gache DR McClay G Manning doi:10.1016/j.ydbio.2006.08.074 Developmental biology, Vol. 300, No. 1. (1 December 2006), pp. 180-193. 2008-06-18T19:29:58-00:00 2006 Developmental biology 0012-1606 300 1 180 193 kinome http://www.citeulike.org/user/renatomilani/article/1306420 <i>PLoS Biol, Vol. 5, No. 3. (13 March 2007)</i><br /><br />The eukaryotic protein kinase (ePK) domain mediates the majority of signaling and coordination of complex events in eukaryotes. By contrast, most bacterial signaling is thought to occur through structurally unrelated histidine kinases, though some ePK-like kinases (ELKs) and small molecule kinases are known in bacteria. Our analysis of the Global Ocean Sampling (GOS) dataset reveals that ELKs are as prevalent as histidine kinases and may play an equally important role in prokaryotic behavior. By combining GOS and public databases, we show that the ePK is just one subset of a diverse superfamily of enzymes built on a common protein kinase-like (PKL) fold. We explored this huge phylogenetic and functional space to cast light on the ancient evolution of this superfamily, its mechanistic core, and the structural basis for its observed diversity. We cataloged 27,677 ePKs and 18,699 ELKs, and classified them into 20 highly distinct families whose known members suggest regulatory functions. GOS data more than tripled the count of ELK sequences and enabled the discovery of novel families and classification and analysis of all ELKs. Comparison between and within families revealed ten key residues that are highly conserved across families. However, all but one of the ten residues has been eliminated in one family or another, indicating great functional plasticity. We show that loss of a catalytic lysine in two families is compensated by distinct mechanisms both involving other key motifs. This diverse superfamily serves as a model for further structural and functional analysis of enzyme evolution. Structural and Functional Diversity of the Microbial Kinome. Natarajan Kannan Susan S Taylor Yufeng Zhai J Craig Venter Gerard Manning doi:10.1371/journal.pbio.0050017 PLoS Biol, Vol. 5, No. 3. (13 March 2007) 2007-05-18T22:47:22-00:00 2007 PLoS Biol 1545-7885 5 3 kinome http://www.citeulike.org/user/renatomilani/article/2906060 <i>WormBook : the online review of C. elegans biology (2005), pp. 1-19.</i><br /><br />Protein kinases are one of the largest and most influential of gene families: constituting some 2% of the proteome, they regulate almost all biochemical pathways and may phosphorylate up to 30% of the proteome. Bioinformatics and comparative genomics were used to determine the C. elegans kinome and put it in evolutionary and functional context. Kinases are deeply conserved in evolution, and the worm has family homologs for over 80% of the human kinome. Almost half of the 438 worm kinases are members of worm-specific or worm-expanded families. Such radiations include genes involved in spermatogenesis, chemosensation, Wnt signaling and FGF receptor-like kinases. The C. briggsae kinome is largely similar apart from the expanded classes, showing that such expansions are evolutionarily recent. Genomic overview of protein kinases. G Manning doi:10.1895/wormbook.1.60.1 WormBook : the online review of C. elegans biology (2005), pp. 1-19. 2008-06-18T19:25:43-00:00 2005 WormBook : the online review of C. elegans biology 1551-8507 1 19 genome kinase kinome http://www.citeulike.org/user/renatomilani/article/90452 <i>Science, Vol. 298, No. 5600. (6 December 2002), pp. 1912-1934.</i><br /><br />We have catalogued the protein kinase complement of the human genome (the "kinome") using public and proprietary genomic, complementary DNA, and expressed sequence tag (EST) sequences. This provides a starting point for comprehensive analysis of protein phosphorylation in normal and disease states, as well as a detailed view of the current state of human genome analysis through a focus on one large gene family. We identify 518 putative protein kinase genes, of which 71 have not previously been reported or described as kinases, and we extend or correct the protein sequences of 56 more kinases. New genes include members of well-studied families as well as previously unidentified families, some of which are conserved in model organisms. Classification and comparison with model organism kinomes identified orthologous groups and highlighted expansions specific to human and other lineages. We also identified 106 protein kinase pseudogenes. Chromosomal mapping revealed several small clusters of kinase genes and revealed that 244 kinases map to disease loci or cancer amplicons. The protein kinase complement of the human genome. G Manning DB Whyte R Martinez T Hunter S Sudarsanam doi:10.1126/science.1075762 Science, Vol. 298, No. 5600. (6 December 2002), pp. 1912-1934. 2005-02-08T22:21:15-00:00 2002 Science 1095-9203 298 5600 1912 1934 genome kinase kinome http://www.citeulike.org/user/renatomilani/article/2805750 <i>PLoS ONE, Vol. 3, No. 2. (2008)</i><br /><br />BACKGROUND: Protein sequence similarity is a commonly used criterion for inferring the unknown function of a protein from a protein of known function. However, proteins can diverge significantly over time such that sequence similarity is difficult, if not impossible, to find. In some cases, a structural similarity remains over long evolutionary time scales and once detected can be used to predict function. METHODOLOGY/PRINCIPAL FINDINGS: Here we employed a high-throughput approach to assign structural and functional annotation to the human proteome, focusing on the collection of human protein kinases, the human kinome. We compared human protein sequences to a library of domains from known structures using WU-BLAST, PSI-BLAST, and 123D. This approach utilized both sequence comparison and fold recognition methods. The resulting set of potential protein kinases was cross-checked against previously identified human protein kinases, and analyzed for conserved kinase motifs. CONCLUSIONS/SIGNIFICANCE: We demonstrate that our structure-based method can be used to identify both typical and atypical human protein kinases. We also identify two potentially novel kinases that contain an interesting combination of kinase and acyl-CoA dehydrogenase domains. Analysis of the human kinome using methods including fold recognition reveals two novel kinases. KM Briedis A Starr PE Bourne doi:10.1371/journal.pone.0001597 PLoS ONE, Vol. 3, No. 2. (2008) 2008-05-16T19:27:43-00:00 2008 PLoS ONE 1932-6203 3 2 bioinformatics kinome methods http://www.citeulike.org/user/renatomilani/article/2805745 <i>Science STKE, Vol. 2002, No. 162. (10 December 2002), 13.</i> Editorial: Focus Issue: The Kinome--Techniques and Methods for Analysis LB Ray NR Gough doi:10.1126/stke.2002.162.eg13 Science STKE, Vol. 2002, No. 162. (10 December 2002), 13. 2008-05-16T19:24:04-00:00 2002 Science STKE 2002 162 13 kinome methods http://www.citeulike.org/user/renatomilani/article/100395 <i>Nature Methods, Vol. 2, No. 3., pp. 225-232.</i> Probing the kinome Laura Bonetta doi:10.1038/nmeth0305-225 Nature Methods, Vol. 2, No. 3., pp. 225-232. 2005-02-22T23:06:47-00:00 Nature Methods 1548-7091 2 3 225 232 Nature Publishing Group kinome methods http://www.citeulike.org/user/renatomilani/article/2758434 <i>Cell, Vol. 133, No. 3. (2 May 2008), pp. 537-548.</i><br /><br />Summary To allow genome-scale identification of genes that regulate cellular signaling, we cloned >90% of all human full-length protein kinase cDNAs and constructed the corresponding kinase activity-deficient mutants. To establish the utility of this resource, we tested the effect of expression of the kinases on three different cellular signaling models. In all screens, many kinases had a modest but significant effect, apparently due to crosstalk between signaling pathways. However, the strongest effects were found with known regulators and novel components, such as MAP3K10 and DYRK2, which we identified in a mammalian Hedgehog (Hh) signaling screen. DYRK2 directly phosphorylated and induced the proteasome-dependent degradation of the key Hh pathway-regulated transcription factor, GLI2. MAP3K10, in turn, affected GLI2 indirectly by modulating the activity of DYRK2 and the known Hh pathway component, GSK3[beta]. Our results establish kinome expression screening as a highly effective way to identify physiological signaling pathway components and genes involved in pathological signaling crosstalk. Application of Active and Kinase-Deficient Kinome Collection for Identification of Kinases Regulating Hedgehog Signaling Markku Varjosalo Mikael Björklund Fang Cheng Heidi Syvänen Teemu Kivioja Sami Kilpinen Zairen Sun Olli Kallioniemi Hendrik Stunnenberg Wei-Wu He Päivi Ojala Jussi Taipale doi:10.1016/j.cell.2008.02.047 Cell, Vol. 133, No. 3. (2 May 2008), pp. 537-548. 2008-05-05T17:16:49-00:00 2008 Cell 133 3 537 548 kinome http://www.citeulike.org/user/renatomilani/article/2678534 <i>Proceedings of the National Academy of Sciences (15 April 2008), 0710814105.</i><br /><br />Janus kinases (JAKs) and signal transducers and activators of transcription (STATs) are essential for responses to interferons (IFNs), most cytokines, and some growth factors. JAK/STAT signaling is not, however, sufficient for a full IFN-gamma response. Here, a convenient, robust, and quantitative flow cytometry-based kinome-wide siRNA screen has identified nine additional kinases as required for the IFN-gamma class II HLA response, seven for an antiviral response, and two for the cytopathic response to encephalomyocarditis virus (EMCV). As one example, inhibition of the IFN-gamma response by siRNA to ataxia telangiectasia-mutated (ATM) differentially affects a spectrum of IFN-gamma-stimulated mRNAs, with inhibitions being seen as early as 1 h after IFN-gamma stimulation. The implication of ATM, with its previously recognized function in chromatin decondensation, in the control of transcription early in the IFN-gamma response highlights both a role for ATM in cytokine responses and a possible correlation with the chromatin decondensation recently observed in response to IFN-gamma in mammalian cells. This work has, therefore, revealed the simplicity, power, and convenience of quantitative flow cytometry-based siRNA screens, a requirement for ATM and multiple additional kinases in the IFN-gamma response and a possible requirement for two of these kinases in the cytopathic response to EMCV. 10.1073/pnas.0710814105 Multiple kinases in the interferon-gamma response D Watling CR Carmo IM Kerr AP Costa-Pereira doi:10.1073/pnas.0710814105 Proceedings of the National Academy of Sciences (15 April 2008), 0710814105. 2008-04-16T17:08:57-00:00 2008 Proceedings of the National Academy of Sciences 0710814105 kinase kinome http://www.citeulike.org/user/renatomilani/article/1105460 <i>Plant Methods, Vol. 3 (12 February 2007), 3.</i> Kinome profiling of Arabidopsis using arrays of kinase consensus substrates Tita Ritsema Jos Joore Wilbert van Workum Corne Pieterse doi:10.1186/1746-4811-3-3 Plant Methods, Vol. 3 (12 February 2007), 3. 2007-02-13T18:07:57-00:00 2007 Plant Methods 1746-4811 3 3 kinase kinome http://www.citeulike.org/user/renatomilani/article/2627644 <i></i> Faculty of 1000 Biology | Kinome profiling of Arabidopsis using arrays of kinase consensus substrates. 2008-04-03T18:26:46-00:00 kinome http://www.citeulike.org/user/renatomilani/article/1411613 <i>Protein and Peptide Letters, Vol. 14, No. 6. (June 2007), pp. 509-517.</i> Comparative Kinomics of Plasmodium Organisms: Unity in Diversity K Anamika N Srinivasan Protein and Peptide Letters, Vol. 14, No. 6. (June 2007), pp. 509-517. 2007-06-25T18:35:05-00:00 2007 Protein and Peptide Letters 0929-8665 14 6 509 517 Bentham Science Publishers kinome malaria http://www.citeulike.org/user/renatomilani/article/2548397 <i>Current Drug Metabolism, Vol. 9, No. 3. (March 2008), pp. 255-258.</i> Kinomics Gomase S Virendra Tagore Somnath doi:10.2174/138920008783884803 Current Drug Metabolism, Vol. 9, No. 3. (March 2008), pp. 255-258. 2008-03-18T04:38:13-00:00 2008 Current Drug Metabolism 1389-2002 9 3 255 258 Bentham Science Publishers kinome omics http://www.citeulike.org/user/renatomilani/article/2503865 <i></i> Single Cell Profiling of Potentiated Phospho-Protein Networks in Cancer Cells 2008-03-10T18:05:54-00:00 cancer kinome http://www.citeulike.org/user/renatomilani/article/2461512 <i></i> Evidence for a Minimal Eukaryotic Phosphoproteome? Sander Diks Kaushal Parikh Marijke van der Sijde Jos Joore Tita Ritsema Maikel Peppelenbosch 2008-03-03T18:33:59-00:00 groningen kinome http://www.citeulike.org/user/renatomilani/article/2461314 <i>J. Biol. Chem., Vol. 279, No. 47. (19 November 2004), pp. 49206-49213.</i><br /><br />The DNA array technique allows comprehensive analysis of the genome and transcriptome, but the high throughput array-based assessment of intracellular signal transduction remains troublesome. The goal of this study was to test a new peptide array technology for studying the activity of all kinases of whole cell lysates, the kinome. Cell lysates from human peripheral blood mononuclear cells before and after stimulation with lipopolysaccharide were used for in vitro phosphorylation with [gamma-33P]ATP arrays consisting of 192 peptides (substrates for kinases) spotted on glass. The usefulness of peptide arrays for studying signal transduction was demonstrated by the generation of the first comprehensive description of the temporal kinetics of phosphorylation events induced by lipopolysaccharide stimulation. Furthermore analysis of the signals obtained suggested activation of p21Ras by lipopolysaccharide, and this was confirmed by direct measurement of p21Ras GTP levels in lipopolysaccharide-stimulated human peripheral blood mononuclear cells, which represents the first direct demonstration of p21Ras activation by stimulation of a Toll receptor family member. Further confidence in the usefulness of peptide array technology for studying signal transduction came from Western blot analysis of lipopolysaccharide-stimulated cells, which corroborated the signals obtained using peptide arrays as well as from the demonstration that kinase inhibitors effected peptide array phosphorylation patterns consistent with the expected action of these inhibitors. We conclude that this first metabolic array is a useful method to determine the enzymatic activities of a large group of kinases, offering high throughput analysis of cellular metabolism and signal transduction. 10.1074/jbc.M405028200 Kinome Profiling for Studying Lipopolysaccharide Signal Transduction in Human Peripheral Blood Mononuclear Cells Sander Diks Klaartje Kok Tom O'Toole Daan Hommes Peter van Dijken Jos Joore Maikel Peppelenbosch doi:10.1074/jbc.M405028200 J. Biol. Chem., Vol. 279, No. 47. (19 November 2004), pp. 49206-49213. 2008-03-03T17:51:27-00:00 2004 J. Biol. Chem. 279 47 49206 49213 groningen kinome pepchip http://www.citeulike.org/user/renatomilani/article/2445121 <i>Cancer Res, Vol. 66, No. 24. (15 December 2006), pp. 11605-11612.</i><br /><br />The precursor metaplastic mucosal lesion that predisposes for esophageal adenocarcinoma is Barrett's esophagus. Because the signal transduction events that occur in Barrett's esophagus are poorly understood, this study aimed at generating a comprehensive description of cellular kinase activity in Barrett's esophagus, normal squamous esophagus, and gastric cardia to gain more insight into the pathogenesis of Barrett's esophagus. Peptide arrays, exhibiting 1,176 specific consensus sequences for protein kinases, were used to produce a global analysis of cellular kinase activity in biopsies of Barrett's esophagus, and results were compared with the neighboring cardia and squamous epithelia. Several differences in kinase activity using immunoblot analysis and enzyme activity assays were validated in biopsies of 27 Barrett's esophagus patients. Three unique kinome profiles are described and compared. We identified cascades of activated kinases showing that mitogen-activated protein kinase and epidermal growth factor receptor activity are both significantly altered in Barrett's esophagus compared with squamous and gastric cardia epithelia. Another novel finding is that the glycolysis pathway is significantly up-regulated in Barrett's esophagus, which is illustrated by an up-regulated pyruvate kinase activity. Here, the unique kinome profile of Barrett's esophagus is made available as a comprehensive database. Several signaling pathways are revealed as specifically expressed in Barrett's esophagus when compared with the adjacent normal epithelia. These unique findings provide novel insight in the pathogenesis of Barrett's esophagus that will ultimately help to resolve the increasing problem of Barrett's esophagus and prevention of esophageal adenocarcinoma. (Cancer Res 2006; 66(24): 11605-12) 10.1158/0008-5472.CAN-06-1370 Comparison of Kinome Profiles of Barrett's Esophagus with Normal Squamous Esophagus and Normal Gastric Cardia Jantine van Baal Sander Diks Ronald Wanders Agnieskza Rygiel Francesca Milano Jos Joore Jacques Bergman Maikel Peppelenbosch Kausilia Krishnadath doi:10.1158/0008-5472.CAN-06-1370 Cancer Res, Vol. 66, No. 24. (15 December 2006), pp. 11605-11612. 2008-02-28T20:05:39-00:00 2006 Cancer Res 66 24 11605 11612 groningen kinome http://www.citeulike.org/user/renatomilani/article/2208356 <i>Nature Biotechnology, Vol. 26, No. 1. (08 January 2008), pp. 127-132.</i> A quantitative analysis of kinase inhibitor selectivity Mazen Karaman Sanna Herrgard Daniel Treiber Paul Gallant Corey Atteridge Brian Campbell Katrina Chan Pietro Ciceri Mindy Davis Philip Edeen Raffaella Faraoni Mark Floyd Jeremy Hunt Daniel Lockhart Zdravko Milanov Michael Morrison Gabriel Pallares Hitesh Patel Stephanie Pritchard Lisa Wodicka Patrick Zarrinkar doi:10.1038/nbt1358 Nature Biotechnology, Vol. 26, No. 1. (08 January 2008), pp. 127-132. 2008-01-08T18:08:00-00:00 2008 Nature Biotechnology 1087-0156 26 1 127 132 Nature Publishing Group kinase kinome