Johannes Balkenhol1, Kristin V Kaltdorf1, Elmina Mammadova-Bach2,3, Attila Braun4, Bernhard Nieswandt2, Marcus Dittrich1,5, Thomas Dandekar6. 1. Functional Genomics and Systems Biology Group, Department of Bioinformatics, Biocenter, Am Hubland, University of Würzburg, D-97074, Würzburg, Germany. 2. Institute of Experimental Biomedicine, University Hospital and Rudolf Virchow Centre, University of Würzburg, Würzburg, Germany. 3. Present address: Division of Nephrology, Department of Medicine IV, Hospital of the Ludwig, Maximilian University of Munich, D-80336, Munich, Germany. 4. Member of the German Center for Lung Research (DZL), Walther-Straub-Institute for Pharmacology and Toxicology, Ludwig-Maximilians University Munich, Munich, Germany. 5. Dept of Genetics, Biocenter, Am Hubland, University of Würzburg, Am Hubland, D 97074, Würzburg, Germany. 6. Functional Genomics and Systems Biology Group, Department of Bioinformatics, Biocenter, Am Hubland, University of Würzburg, D-97074, Würzburg, Germany. dandekar@biozentrum.uni-wuerzburg.de.
Abstract
BACKGROUND: Understanding the molecular mechanisms of platelet activation and aggregation is of high interest for basic and clinical hemostasis and thrombosis research. The central platelet protein interaction network is involved in major responses to exogenous factors. This is defined by systemsbiological pathway analysis as the central regulating signaling cascade of platelets (CC). RESULTS: The CC is systematically compared here between mouse and human and major differences were found. Genetic differences were analysed comparing orthologous human and mouse genes. We next analyzed different expression levels of mRNAs. Considering 4 mouse and 7 human high-quality proteome data sets, we identified then those major mRNA expression differences (81%) which were supported by proteome data. CC is conserved regarding genetic completeness, but we observed major differences in mRNA and protein levels between both species. Looking at central interactors, human PLCB2, MMP9, BDNF, ITPR3 and SLC25A6 (always Entrez notation) show absence in all murine datasets. CC interactors GNG12, PRKCE and ADCY9 occur only in mice. Looking at the common proteins, TLN1, CALM3, PRKCB, APP, SOD2 and TIMP1 are higher abundant in human, whereas RASGRP2, ITGB2, MYL9, EIF4EBP1, ADAM17, ARRB2, CD9 and ZYX are higher abundant in mouse. Pivotal kinase SRC shows different regulation on mRNA and protein level as well as ADP receptor P2RY12. CONCLUSIONS: Our results highlight species-specific differences in platelet signaling and points of specific fine-tuning in human platelets as well as murine-specific signaling differences.
BACKGROUND: Understanding the molecular mechanisms of platelet activation and aggregation is of high interest for basic and clinical hemostasis and thrombosis research. The central platelet protein interaction network is involved in major responses to exogenous factors. This is defined by systemsbiological pathway analysis as the central regulating signaling cascade of platelets (CC). RESULTS: The CC is systematically compared here between mouse and human and major differences were found. Genetic differences were analysed comparing orthologous human and mouse genes. We next analyzed different expression levels of mRNAs. Considering 4 mouse and 7 human high-quality proteome data sets, we identified then those major mRNA expression differences (81%) which were supported by proteome data. CC is conserved regarding genetic completeness, but we observed major differences in mRNA and protein levels between both species. Looking at central interactors, humanPLCB2, MMP9, BDNF, ITPR3 and SLC25A6 (always Entrez notation) show absence in all murine datasets. CC interactors GNG12, PRKCE and ADCY9 occur only in mice. Looking at the common proteins, TLN1, CALM3, PRKCB, APP, SOD2 and TIMP1 are higher abundant in human, whereas RASGRP2, ITGB2, MYL9, EIF4EBP1, ADAM17, ARRB2, CD9 and ZYX are higher abundant in mouse. Pivotal kinase SRC shows different regulation on mRNA and protein level as well as ADP receptor P2RY12. CONCLUSIONS: Our results highlight species-specific differences in platelet signaling and points of specific fine-tuning in human platelets as well as murine-specific signaling differences.
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