ArticleThe Journal of biological chemistry2009
Protein kinase C-mediated phosphorylation and activation of PDE3A regulate cAMP levels in human platelets.
Article in The Journal of biological chemistry, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed, 81 citations in OpenAlex.
- Pan-cancer ex vivo target evaluation of phosphodiesterase 3 A (PDE3A).Journal of molecular medicine (Berlin, Germany) · 2026Article
- Differential regulation of cyclic adenosine monophosphate by phosphodiesterase 3A discriminates thrombin-induced protease activated receptor 1- and 4-dependent platelet activation.Journal of thrombosis and haemostasis : JTH · 2026Article
- Review
- The Role of PDE3A in Cancer.ACS omega · 2026Review
- Review
- Nanodomain cAMP signaling in cardiac pathophysiology: potential for developing targeted therapeutic interventions.Physiological reviews · 2025Review
- Article
- Identification and functional study of genetic polymorphisms in cyclic nucleotide phosphodiesterase 3A (PDE3A).Annals of human genetics · 2021Article
- Mechanistic insights into cancer cell killing through interaction of phosphodiesterase 3A and schlafen family member 12.The Journal of biological chemistry · 2020Article
- Atherogenic lipid stress induces platelet hyperactivity through CD36-mediated hyposensitivity to prostacyclin: the role of phosphodiesterase 3A.Haematologica · 2020Article
- Akt-mediated platelet apoptosis and its therapeutic implications in immune thrombocytopenia.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- cUMP hydrolysis by PDE3B.Naunyn-Schmiedeberg's archives of pharmacology · 2018Article
- Cyclic nucleotide-dependent inhibitory signaling interweaves with activating pathways to determine platelet responses.Research and practice in thrombosis and haemostasis · 2018Review
- Review
- Functions of PDE3 Isoforms in Cardiac Muscle.Journal of cardiovascular development and disease · 2018Review
- The norpurpureine alkaloid fromCellular & molecular biology letters · 2018Article
- Article
- A map of human circular RNAs in clinically relevant tissues.Journal of molecular medicine (Berlin, Germany) · 2017Article
- Phosphorylation of mycobacterial phosphodiesterase by eukaryotic-type Ser/Thr kinase controls its two distinct and mutually exclusive functionalities.The Journal of biological chemistry · 2017Article
- Effects of phosphodiesterase 3A modulation on murine cerebral microhemorrhages.Journal of neuroinflammation · 2017Article
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
The elevation of [cAMP](i) is an important mechanism of platelet inhibition and is regulated by the opposing activity of adenylyl cyclase and phosphodiesterase (PDE). In this study, we demonstrate that a variety of platelet agonists, including thrombin, significantly enhance the activity of PDE3A in a phosphorylation-dependent manner. Stimulation of platelets with the PAR-1 agonist SFLLRN resulted in rapid and transient phosphorylation of PDE3A on Ser(312), Ser(428), Ser(438), Ser(465), and Ser(492), in parallel with the PKC (protein kinase C) substrate, pleckstrin. Furthermore, phosphorylation and activation of PDE3A required the activation of PKC, but not of PI3K/PKB, mTOR/p70S6K, or ERK/RSK. Activation of PKC by phorbol esters also resulted in phosphorylation of the same PDE3A sites in a PKC-dependent, PKB-independent manner. This was further supported by the finding that IGF-1, which strongly activates PI3K/PKB, but not PKC, did not regulate PDE3A. Platelet activation also led to a PKC-dependent association between PDE3A and 14-3-3 proteins. In contrast, cAMP-elevating agents such as PGE(1) and forskolin-induced phosphorylation of Ser(312) and increased PDE3A activity, but did not stimulate 14-3-3 binding. Finally, complete antagonism of PGE(1)-evoked cAMP accumulation by thrombin required both G(i) and PKC activation. Together, these results demonstrate that platelet activation stimulates PKC-dependent phosphorylation of PDE3A on Ser(312), Ser(428), Ser(438), Ser(465), and Ser(492) leading to a subsequent increase in cAMP hydrolysis and 14-3-3 binding.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.