6533b858fe1ef96bd12b5acd

RESEARCH PRODUCT

Time-resolved characterization of cAMP/PKA-dependent signaling reveals that platelet inhibition is a concerted process involving multiple signaling pathways

Marc VaudelRené P. ZahediJohannes VeitJoerg GeigerPeter NollauStepan GambaryanFlorian BeckAlbert SickmannAlbert SickmannLennart MartensLennart MartensUlrich WalterOliver Kohlbacher

subject

Blood PlateletsImmunologyProstacyclinBiologyBiochemistrychemistry.chemical_compoundCyclic AMPmedicineHumansCyclic adenosine monophosphateIloprostProtein Interaction MapsPlatelet activationPhosphorylationProtein kinase AKinaseCell BiologyHematologyPlatelet ActivationCyclic AMP-Dependent Protein KinaseschemistryBiochemistryPlatelet aggregation inhibitorPhosphorylationSignal transductionPlatelet Aggregation InhibitorsSignal Transductionmedicine.drug

description

One of the most important physiological platelet inhibitors is endothelium-derived prostacyclin which stimulates the platelet cyclic adenosine monophosphate/protein kinase A (cAMP/PKA)-signaling cascade and inhibits virtually all platelet-activating key mechanisms. Using quantitative mass spectrometry, we analyzed time-resolved phosphorylation patterns in human platelets after treatment with iloprost, a stable prostacyclin analog, for 0, 10, 30, and 60 seconds to characterize key mediators of platelet inhibition and activation in 3 independent biological replicates. We quantified over 2700 different phosphorylated peptides of which 360 were significantly regulated upon stimulation. This comprehensive and time-resolved analysis indicates that platelet inhibition is a multipronged process involving different kinases and phosphatases as well as many previously unanticipated proteins and pathways.

yearjournalcountryeditionlanguage
2014-01-30Blood
https://doi.org/10.1182/blood-2013-07-512384