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dc.contributor.authorRoberts, Wayne*
dc.contributor.authorMagwenzi, S.*
dc.contributor.authorAburima, Ahmed*
dc.contributor.authorNaseem, Khalid M.*
dc.date.accessioned2014-04-28T11:18:21Z
dc.date.available2014-04-28T11:18:21Z
dc.date.issued2010
dc.identifier.citationRoberts, W., Magwenzi, S., Aburima, A., Naseem, K. M. (2010) Thrombospondin-1 induces platelet activation through CD36-dependent inhibition of the cAMP/protein kinase A signaling cascade. Blood, 116(20), 4297-4306.
dc.identifier.urihttp://hdl.handle.net/10454/6155
dc.description.abstractCyclic adenosine monophosphate (cAMP)-dependent signaling modulates platelet function at sites of vascular injury. Here we show that thrombospondin-1 (TSP-1) prevents cAMP/protein kinase A (PKA) signaling through a CD36-dependent mechanism. Prostaglandin E(1) (PGE(1)) induced a robust inhibition of both platelet aggregation and platelet arrest under physiologic conditions of flow. Exogenous TSP-1 reduced significantly PGE(1)-mediated inhibition of both platelet aggregation and platelet arrest. TSP-1 prevented PGE(1)-stimulated cAMP accrual and phosphorylation of PKA substrates, through a mechanism requiring phosphodiesterase3A. TSP-1 also inhibited VASP phosphorylation stimulated by the nonhydrolyzable cAMP analog, 8-bromo-cAMP, indicating that it may regulate cAMP-mediated activation of PKA. The inhibitory effect of TSP-1 on cAMP signaling could be reproduced with a peptide possessing a CD36 binding sequence of TSP-1, while the effects of TSP-1 were prevented by a CD36 blocking antibody. TSP-1 and the CD36 binding peptide induced phosphorylation of Src kinases, p38 and JNK. Moreover, inhibition of Src kinases blocked TSP-1-mediated regulation of cAMP concentrations and the phosphorylation of VASP, indicating that TSP-1 modulated the cAMP/PKA signaling events through a tyrosine kinase-dependent pathway downstream of CD36. These data reveal a new role for TSP-1 in promoting platelet aggregation through modulation of the cAMP-PKA signaling pathway.
dc.relation.isreferencedbyhttp://dx.doi.org/10.1182/blood-2010-01-265561
dc.subjectAdenylate Cyclase; Antagonists & inhibitors;
dc.subjectAlprostadil; pharmacology;
dc.subjectAntigens; CD36; Metabolism;
dc.subjectBlood platelets; Cytology; Drug effects; Enzymology;
dc.subjectCyclic AMP;
dc.subjectCyclic AMP-dependent protein kinases;
dc.subjectEnzyme activation;
dc.subjectHemorheology;
dc.subjectHumans;
dc.subjectPeptides;
dc.subjectPlatelet activation;
dc.subjectPlatelet aggregation;
dc.subjectProtein binding;
dc.subjectSignal transduction;
dc.subjectThrombospondin 1;
dc.subjectsrc-Family kinases;
dc.subjectREF 2014
dc.titleThrombospondin-1 induces platelet activation through CD36-dependent inhibition of the cAMP/protein kinase A signaling cascade
dc.typeArticle


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