Time-resolved characterization of cAMP/PKA-dependent signaling reveals that platelet inhibition is a concerted process involving multiple signaling pathways
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Time-resolved characterization of cAMP/PKA-dependent signaling reveals that platelet inhibition is a concerted process involving multiple signaling pathways. / Beck, Florian; Geiger, Jörg; Gambaryan, Stepan; Veit, Johannes; Vaudel, Marc; Nollau, Peter; Kohlbacher, Oliver; Martens, Lennart; Walter, Ulrich; Sickmann, Albert; Zahedi, René P.
in: BLOOD, Jahrgang 123, Nr. 5, 30.01.2014, S. e1-e10.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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T1 - Time-resolved characterization of cAMP/PKA-dependent signaling reveals that platelet inhibition is a concerted process involving multiple signaling pathways
AU - Beck, Florian
AU - Geiger, Jörg
AU - Gambaryan, Stepan
AU - Veit, Johannes
AU - Vaudel, Marc
AU - Nollau, Peter
AU - Kohlbacher, Oliver
AU - Martens, Lennart
AU - Walter, Ulrich
AU - Sickmann, Albert
AU - Zahedi, René P
PY - 2014/1/30
Y1 - 2014/1/30
N2 - 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.
AB - 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.
KW - Blood Platelets
KW - Cyclic AMP
KW - Cyclic AMP-Dependent Protein Kinases
KW - Humans
KW - Iloprost
KW - Phosphorylation
KW - Platelet Activation
KW - Platelet Aggregation Inhibitors
KW - Protein Interaction Maps
KW - Signal Transduction
U2 - 10.1182/blood-2013-07-512384
DO - 10.1182/blood-2013-07-512384
M3 - SCORING: Journal article
C2 - 24324209
VL - 123
SP - e1-e10
JO - BLOOD
JF - BLOOD
SN - 0006-4971
IS - 5
ER -