title: Time-resolved characterization of cAMP/PKA-dependent signaling reveals that platelet inhibition is a concerted process involving multiple signaling pathways.
abstract: 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.
authors: Leibniz-Institut für Analytische Wissenschaften-ISAS-e.V., Dortmund, Germany;
authors: Florian
authors: F
authors: Beck
authors: Jörg
authors: J
authors: Geiger
authors: Stepan
authors: S
authors: Gambaryan
authors: Johannes
authors: J
authors: Veit
authors: Marc
authors: M
authors: Vaudel
authors: Peter
authors: P
authors: Nollau
authors: Oliver
authors: O
authors: Kohlbacher
authors: Lennart
authors: L
authors: Martens
authors: Ulrich
authors: U
authors: Walter
authors: Albert
authors: A
authors: Sickmann
authors: René P
authors: RP
authors: Zahedi
mesh_terms: D001792:Blood Platelets / Q000166:cytology / Q000187:drug effects*; D000242:Cyclic AMP / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism*; D006801:Humans; D016285:Iloprost / Q000494:pharmacology*; D010766:Phosphorylation / Q000187:drug effects; D015539:Platelet Activation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D060066:Protein Interaction Maps / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D010975:Platelet Aggregation Inhibitors; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D016285:Iloprost