TY  - JOUR
A1  - Balkenhol, Johannes
A1  - Kaltdorf, Kristin V.
A1  - Mammadova-Bach, Elmina
A1  - Braun, Attila
A1  - Nieswandt, Bernhard
A1  - Dittrich, Marcus
A1  - Dandekar, Thomas
T1  - Comparison of the central human and mouse platelet signaling cascade by systems biological analysis
JF  - BMC Genomics
N2  - 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.
KW  - interspecies comparison
KW  - transcriptome
KW  - proteome
KW  - platelet
KW  - network
KW  - signaling
KW  - mouse
KW  - human
KW  - interactome
KW  - cascade
Y1  - 2020
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-230377
VL  - 21
ER  -