Phosphoproteome of resting human platelets.
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]
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
Name UniProt ID Coagulation factor V P12259 Details High affinity immunoglobulin epsilon receptor subunit gamma P30273 Details Pyruvate kinase PKM P14618 Details Synaptic vesicular amine transporter Q05940 Details 5'-AMP-activated protein kinase subunit beta-1 Q9Y478 Details Beta-adrenergic receptor kinase 1 P25098 Details Acetyl-coenzyme A synthetase, cytoplasmic Q9NR19 Details cGMP-inhibited 3',5'-cyclic phosphodiesterase A Q14432 Details Fibrinogen alpha chain P02671 Details Pyruvate dehydrogenase E1 component subunit alpha, somatic form, mitochondrial P08559 Details Glycine dehydrogenase (decarboxylating), mitochondrial P23378 Details Cytosolic phospholipase A2 P47712 Details 5'-AMP-activated protein kinase catalytic subunit alpha-1 Q13131 Details Sodium/hydrogen exchanger 1 P19634 Details Proto-oncogene tyrosine-protein kinase Src P12931 Details Tyrosine-protein kinase Fyn P06241 Details Protein-tyrosine kinase 2-beta Q14289 Details Protein kinase C beta type P05771 Details CTP synthase 1 P17812 Details Phospholipid-transporting ATPase IA Q9Y2Q0 Details Calnexin P27824 Details Mitogen-activated protein kinase 14 Q16539 Details Platelet glycoprotein Ib alpha chain P07359 Details Vitronectin P04004 Details Heat shock protein HSP 90-alpha P07900 Details Protein kinase C alpha type P17252 Details Integrin beta-3 P05106 Details Catalase P04040 Details cAMP-specific 3',5'-cyclic phosphodiesterase 4D Q08499 Details Tyrosine-protein kinase SYK P43405 Details Tubulin alpha-4A chain P68366 Details Heat shock protein HSP 90-beta P08238 Details Synaptotagmin-like protein 4 Q96C24 Details Procollagen-lysine,2-oxoglutarate 5-dioxygenase 2 O00469 Details Phosphatidylserine synthase 2 Q9BVG9 Details Protein kinase C delta type Q05655 Details Voltage-dependent anion-selective channel protein 1 P21796 Details Voltage-dependent anion-selective channel protein 2 P45880 Details Prostaglandin E synthase 3 Q15185 Details Wiskott-Aldrich syndrome protein P42768 Details Mitogen-activated protein kinase 13 O15264 Details cAMP-dependent protein kinase type II-alpha regulatory subunit P13861 Details cAMP-dependent protein kinase type I-alpha regulatory subunit P10644 Details Heat shock protein beta-1 P04792 Details Microtubule-associated protein 4 P27816 Details Serine/threonine-protein kinase Nek2 P51955 Details Serine/threonine-protein phosphatase PP1-alpha catalytic subunit P62136 Details Tyrosine-protein kinase Lyn P07948 Details Spectrin beta chain, non-erythrocytic 1 Q01082 Details Breakpoint cluster region protein P11274 Details Dual specificity mitogen-activated protein kinase kinase 2 P36507 Details Mitogen-activated protein kinase kinase kinase 2 Q9Y2U5 Details RalA-binding protein 1 Q15311 Details Membrane-associated progesterone receptor component 1 O00264 Details Hepatoma-derived growth factor P51858 Details Huntingtin P42858 Details Alpha-2-HS-glycoprotein P02765 Details Filamin-A P21333 Details Transgelin-2 P37802 Details Zyxin Q15942 Details Myosin-9 P35579 Details STE20/SPS1-related proline-alanine-rich protein kinase Q9UEW8 Details Serine/threonine-protein kinase TAO1 Q7L7X3 Details TRAF2 and NCK-interacting protein kinase Q9UKE5 Details Serine/threonine-protein kinase MARK2 Q7KZI7 Details CLIP-associating protein 1 Q7Z460 Details Misshapen-like kinase 1 Q8N4C8 Details Myosin light chain kinase, smooth muscle Q15746 Details Serine/threonine-protein kinase PAK 2 Q13177 Details Serine/threonine-protein kinase 10 O94804 Details P2Y purinoceptor 1 P47900 Details ATP-citrate synthase P53396 Details Zinc transporter SLC39A7 Q92504 Details Tyrosine-protein phosphatase non-receptor type 12 Q05209 Details Interleukin-6 receptor subunit beta P40189 Details