Phosphoproteome of resting human platelets.

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Zahedi RP, Lewandrowski U, Wiesner J, Wortelkamp S, Moebius J, Schutz C, Walter U, Gambaryan S, Sickmann A

Phosphoproteome of resting human platelets.

J Proteome Res. 2008 Feb;7(2):526-34. Epub 2007 Dec 19.

PubMed ID
18088087 [ View in PubMed
]
Abstract

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.

DrugBank Data that Cites this Article

Polypeptides
NameUniProt ID
Coagulation factor VP12259Details
High affinity immunoglobulin epsilon receptor subunit gammaP30273Details
Pyruvate kinase PKMP14618Details
Synaptic vesicular amine transporterQ05940Details
5'-AMP-activated protein kinase subunit beta-1Q9Y478Details
Beta-adrenergic receptor kinase 1P25098Details
Acetyl-coenzyme A synthetase, cytoplasmicQ9NR19Details
cGMP-inhibited 3',5'-cyclic phosphodiesterase AQ14432Details
Fibrinogen alpha chainP02671Details
Pyruvate dehydrogenase E1 component subunit alpha, somatic form, mitochondrialP08559Details
Glycine dehydrogenase (decarboxylating), mitochondrialP23378Details
Cytosolic phospholipase A2P47712Details
5'-AMP-activated protein kinase catalytic subunit alpha-1Q13131Details
Sodium/hydrogen exchanger 1P19634Details
Proto-oncogene tyrosine-protein kinase SrcP12931Details
Tyrosine-protein kinase FynP06241Details
Protein-tyrosine kinase 2-betaQ14289Details
Protein kinase C beta typeP05771Details
CTP synthase 1P17812Details
Phospholipid-transporting ATPase IAQ9Y2Q0Details
CalnexinP27824Details
Mitogen-activated protein kinase 14Q16539Details
Platelet glycoprotein Ib alpha chainP07359Details
VitronectinP04004Details
Heat shock protein HSP 90-alphaP07900Details
Protein kinase C alpha typeP17252Details
Integrin beta-3P05106Details
CatalaseP04040Details
cAMP-specific 3',5'-cyclic phosphodiesterase 4DQ08499Details
Tyrosine-protein kinase SYKP43405Details
Tubulin alpha-4A chainP68366Details
Heat shock protein HSP 90-betaP08238Details
Synaptotagmin-like protein 4Q96C24Details
Procollagen-lysine,2-oxoglutarate 5-dioxygenase 2O00469Details
Phosphatidylserine synthase 2Q9BVG9Details
Protein kinase C delta typeQ05655Details
Voltage-dependent anion-selective channel protein 1P21796Details
Voltage-dependent anion-selective channel protein 2P45880Details
Prostaglandin E synthase 3Q15185Details
Wiskott-Aldrich syndrome proteinP42768Details
Mitogen-activated protein kinase 13O15264Details
cAMP-dependent protein kinase type II-alpha regulatory subunitP13861Details
cAMP-dependent protein kinase type I-alpha regulatory subunitP10644Details
Heat shock protein beta-1P04792Details
Microtubule-associated protein 4P27816Details
Serine/threonine-protein kinase Nek2P51955Details
Serine/threonine-protein phosphatase PP1-alpha catalytic subunitP62136Details
Tyrosine-protein kinase LynP07948Details
Spectrin beta chain, non-erythrocytic 1Q01082Details
Breakpoint cluster region proteinP11274Details
Dual specificity mitogen-activated protein kinase kinase 2P36507Details
Mitogen-activated protein kinase kinase kinase 2Q9Y2U5Details
RalA-binding protein 1Q15311Details
Membrane-associated progesterone receptor component 1O00264Details
Hepatoma-derived growth factorP51858Details
HuntingtinP42858Details
Alpha-2-HS-glycoproteinP02765Details
Filamin-AP21333Details
Transgelin-2P37802Details
ZyxinQ15942Details
Myosin-9P35579Details
STE20/SPS1-related proline-alanine-rich protein kinaseQ9UEW8Details
Serine/threonine-protein kinase TAO1Q7L7X3Details
TRAF2 and NCK-interacting protein kinaseQ9UKE5Details
Serine/threonine-protein kinase MARK2Q7KZI7Details
CLIP-associating protein 1Q7Z460Details
Misshapen-like kinase 1Q8N4C8Details
Myosin light chain kinase, smooth muscleQ15746Details
Serine/threonine-protein kinase PAK 2Q13177Details
Serine/threonine-protein kinase 10O94804Details
P2Y purinoceptor 1P47900Details
ATP-citrate synthaseP53396Details
Zinc transporter SLC39A7Q92504Details
Tyrosine-protein phosphatase non-receptor type 12Q05209Details
Interleukin-6 receptor subunit betaP40189Details
Adenylate cyclase type 6O43306Details