Phosphoproteome of resting human platelets.
Beside their main physiological function in hemostasis, platelets are also highly involved in pathological processes, such as atherothrombosis and inflammation. During hemostasis, binding of adhesive substrates to tyrosine-kinase-linked adhesion receptors and/or soluble agonists to G-protein coupled receptors leads to a cascade of intracellular signaling processes based on substrate (de)phosphorylation. The same mechanisms are involved in platelet activation at sites of atherosclerotic plaque rupture, contributing to vessel occlusion and consequently to pathologic states, such as myocardial infarction, stroke, or peripheral artery disease. To gain a deeper insight into platelet function, we analyzed the phosphoproteome of resting platelets and identified 564 phosphorylation sites from more than 270 proteins, of which many have not been described in platelets before. Among those were several unknown potential protein kinase A (PKA) and protein kinase G (PKG) substrates. Because platelet inhibition is tightly regulated especially by PKA and PKG activity, these proteins may represent important new targets for cardiovascular research. Thus, our finding that GPIbalpha is phosphorylated at Ser603 in resting platelets may represent a novel mechanism for the regulation of one of the most important platelet receptor (GPIb-IX-V) mediated signaling pathways by PKA/PKG.
Zahedi
René P
RP
Rudolf Virchow Center/DFG Research Center for Experimental Biomedicine, University of Würzburg, Protein Mass Spectrometry and Functional Proteomics Group, Würzburg, D-97078 Germany.
Lewandrowski
Urs
U
Wiesner
Julia
J
Wortelkamp
Stefanie
S
Moebius
Jan
J
Schütz
Claudia
C
Walter
Ulrich
U
Gambaryan
Stepan
S
Sickmann
Albert
A
D001792:Blood Platelets / Q000166:cytology / Q000378:metabolism*; D002846:Chromatography, Affinity; D002852:Chromatography, Ion Exchange; D006801:Humans; D010748:Phosphopeptides / Q000097:blood / Q000145:classification; D010750:Phosphoproteins / Q000097:blood* / Q000145:classification; D010766:Phosphorylation; D015539:Platelet Activation / Q000502:physiology; D020543:Proteome / Q000378:metabolism*; D016192:Resting Phase, Cell Cycle / Q000502:physiology*; D053719:Tandem Mass Spectrometry
D010748:Phosphopeptides; D010750:Phosphoproteins; D020543:Proteome